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OBJECTIVE: This study aimed to prospectively investigate associations of working night shifts with weight gain in the Nightingale Study, a large cohort of female nurses. METHODS: This study included 36 273 registered nurses, who completed questionnaires in 2011 and 2017. Cumulative number of nights, mean number of nights/month and consecutive number of nights/month in 2007–2011 were assessed. We used Poisson regression to estimate multivariable-adjusted incidence rate ratios (IRR) of >5% weight gain from 2011 to 2017 among all participants and assess risk of development of overweight/obesity (BMI≥25 kg/m 2 ) among women with healthy baseline body mass index. The reference group consisted of women who never worked nights. RESULTS: Overall, working night shifts in 2007–2011 was associated with >5% weight gain [IRR 1.07, 95% confidence interval (CI) 1.01–1.13]. Associations differed by menopausal status in 2011, with an increased risk of gaining >5% weight limited to postmenopausal women who worked nights (IRR 1.23, 95% CI 1.10–1.38). Postmenopausal women had an increased risk of >5% weight gain when they worked on average ≥4 nights/month (4–5: IRR 1.29, 95% CI 1.09–1.52, ≥6: IRR 1.27, 95% CI 1.11–1.47) or ≥4 consecutive nights/month (IRR 1.37, 95% CI 1.19–1.58), compared to postmenopausal women who never worked nights. For postmenopausal women with healthy weight at baseline, night shift work was associated with an increased risk of overweight/obesity at follow-up (IRR 1.24, 95% CI 1.03–1.50). CONCLUSIONS: Working night shifts was associated with a slightly increased risk of weight gain and overweight/obesity development among women who were postmenopausal at study inclusion. Our findings emphasize the importance of health promotion to maintain a healthy weight among (postmenopausal) night workers.

Female survivors of childhood, adolescent, and young adult (CAYA) cancer who were given radiation to fields that include breast tissue (ie, chest radiation) have an increased risk of breast cancer. Clinical practice guidelines are essential to ensure that these individuals receive optimum care and to reduce the detrimental consequences of cancer treatment; however, surveillance recommendations vary among the existing long-term follow-up guidelines. We applied evidence-based methods to develop international, harmonised recommendations for breast cancer surveillance among female survivors of CAYA cancer who were given chest radiation before age 30 years. The recommendations were formulated by an international, multidisciplinary panel and are graded according to the strength of the underlying evidence.

Despite efforts to reduce the incidence of second cancer, the risk was not lower among 5-year survivors of Hodgkin's lymphoma in the Netherlands treated between 1989 and 2000, a period when more limited radiation fields and doses were used, than in earlier periods. Since the late 1960s, when combination chemotherapy and high-energy radiation therapy were introduced for the treatment of Hodgkin’s lymphoma, survival has increased dramatically. Cure has come at a price, however, because the treatment of Hodgkin’s lymphoma has been shown to increase the risk of subsequent malignant neoplasms and other late effects considerably. 1 – 22 Although very high relative risks have been observed for leukemia (especially among patients who were treated with alkylating agents) and non-Hodgkin’s lymphoma (which was not previously associated with a particular type of therapy), second solid cancers, the occurrence of which is related primarily to radiation therapy, contribute . . .

Conflicting conclusions have been published regarding breast cancer survival of BRCA1/2 mutation carriers. Here we provide an evidence-based systematic literature review. Eligible publications were observational studies assessing the survival of breast cancer patients carrying a BRCA1/2 mutation compared to non-carriers or the general breast cancer population. We performed meta-analyses and best-evidence syntheses for survival outcomes taking into account study quality assessed by selection bias, misclassification bias and confounding. Sixty-six relevant studies were identified. Moderate evidence for a worse unadjusted recurrence-free survival for BRCA1 mutation carriers was found. For BRCA1 and BRCA2 there was a tendency towards a worse breast cancer-specific and overall survival, however, results were heterogeneous and the evidence was judged to be indecisive. Surprisingly, only 8 studies considered adjuvant treatment as a confounder or effect modifier while only two studies took prophylactic surgery into account. Adjustment for tumour characteristics tended to shift the observed risk estimates towards a relatively more favourable survival. In contrast to currently held beliefs of some oncologists, current evidence does not support worse breast cancer survival of BRCA1/2 mutation carriers in the adjuvant setting; differences if any are likely to be small. More well-designed studies are awaited.

ObjectivesNight shift work has been classified as probably carcinogenic to humans, possibly related to suppression of melatonin secretion. Although experimental studies suggest that melatonin inhibits intestinal tumor proliferation, epidemiological evidence for a relationship between night shift work and colorectal cancer (CRC) risk is lacking.MethodsWe prospectively examined the association between night shift work and CRC in the Nightingale Study. We included 56 477 Dutch female nurses who completed a questionnaire in 2011, including occupational history with detailed (historical) information on night shift work. Until February 2025, 468 incident CRCs were recorded. Age-adjusted HRs and 95% CIs for associations between night shift work variables and CRC risk were estimated using Cox regressions.ResultsCRC risk did not differ between nurses who ever or never worked night shifts (HR=1.13; 95% CI=0.89 to 1.44). A longer duration of working night shifts (≥20 years: HR=1.19; 95%CI=0.89 to 1.60) was neither associated with CRC risk. However, a higher average number of consecutive night shifts per month (continuous per shift; HR=1.04, 95%CI=1.00 to 1.07) and a higher cumulative number of performed night shifts (continuous per 250 shifts: HR=1.02; 95%CI=1.00 to 1.04) were associated with a slightly increased risk. Chronotype did not affect the associations of CRC risk with night shift work.ConclusionsAlthough a longer duration of night shift work was not associated with CRC risk, both a higher frequency of and a higher cumulative exposure to night shifts were associated with slightly higher risk, suggesting a potential association between extensive exposure to night shift work and CRC risk.

Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate mortality for patients with the major subtypes of breast cancer as classified using five immunohistochemical markers, to investigate patterns of mortality over time, and to test for heterogeneity by subtype. We pooled data from more than 10,000 cases of invasive breast cancer from 12 studies that had collected information on hormone receptor status, human epidermal growth factor receptor-2 (HER2) status, and at least one basal marker (cytokeratin [CK]5/6 or epidermal growth factor receptor [EGFR]) together with survival time data. Tumours were classified as luminal and nonluminal tumours according to hormone receptor expression. These two groups were further subdivided according to expression of HER2, and finally, the luminal and nonluminal HER2-negative tumours were categorised according to expression of basal markers. Changes in mortality rates over time differed by subtype. In women with luminal HER2-negative subtypes, mortality rates were constant over time, whereas mortality rates associated with the luminal HER2-positive and nonluminal subtypes tended to peak within 5 y of diagnosis and then decline over time. In the first 5 y after diagnosis the nonluminal tumours were associated with a poorer prognosis, but over longer follow-up times the prognosis was poorer in the luminal subtypes, with the worst prognosis at 15 y being in the luminal HER2-positive tumours. Basal marker expression distinguished the HER2-negative luminal and nonluminal tumours into different subtypes. These patterns were independent of any systemic adjuvant therapy. The six subtypes of breast cancer defined by expression of five markers show distinct behaviours with important differences in short term and long term prognosis. Application of these markers in the clinical setting could have the potential to improve the targeting of adjuvant chemotherapy to those most likely to benefit. The different patterns of mortality over time also suggest important biological differences between the subtypes that may result in differences in response to specific therapies, and that stratification of breast cancers by clinically relevant subtypes in clinical trials is urgently required.

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have increased cancer risk. Platinum retention in healthy tissue may contribute to carcinogenesis. We assessed total platinum concentrations in plasma, urine, and normal colonic mucosa samples in TCS treated with cisplatin. From the total TCS treated with ≥3 cycles cisplatin who participated in a colonoscopy-screening study in four Dutch hospitals (n = 154), plasma (n = 131) and urine (n = 115) samples were collected. During colonoscopy, 60 biopsies of normal colonic mucosa (two samples each per 30 randomly selected patients undergoing colonoscopy) were obtained. Samples were analyzed for total platinum concentrations using inductively coupled plasma mass spectrometry and compared with controls (plasma: 10, urine: 3, normal colonic mucosa: 9). The median age at colonoscopy was 50 years (interquartile range (IQR): 43–57) and the median time since treatment was 20 years (IQR:16–26). Median platinum concentrations in plasma (38 pg/mL; IQR: 24–61 pg/mL) and urine (376 pg/mL; IQR: 208–698 pg/mL) remained elevated in TCS up to 40 years post-treatment and were higher than in controls (all controls were below limits of detection [plasma: 25 pg/mL, urine: 6 pg/mL]). The median platinum concentration in normal colonic mucosa was 0.58 pg/mg (IQR: 0.33–1.59 pg/mg) in the transverse and 0.51 pg/mg (IQR:0.26–1.25 pg/mg) in the descending colon. Cisplatin treatment is associated with long-term retention of platinum in various patient sample types. This might increase cancer risk by causing somatic mutations, potentially explaining the elevated risk of second malignant neoplasms in TCS. The long-term effects of platinum retention should be monitored to understand carcinogenesis and to provide guidelines for early second cancer detection. Trial registration: ClinicalTrials.Gov: NCT04180033 .

Background The incidence and mortality of endometrial cancer (EC) is on the rise. Eighty-five percent of ECs depend on estrogen receptor alpha (ERα) for proliferation, but little is known about its transcriptional regulation in these tumors. Results We generate epigenomics, transcriptomics, and Hi-C datastreams in healthy and tumor endometrial tissues, identifying robust ERα reprogramming and profound alterations in 3D genome organization that lead to a gain of tumor-specific enhancer activity during EC development. Integration with endometrial cancer risk single-nucleotide polymorphisms and whole-genome sequencing data from primary tumors and metastatic samples reveals a striking enrichment of risk variants and non-coding somatic mutations at tumor-enriched ERα sites. Through machine learning-based predictions and interaction proteomics analyses, we identify an enhancer mutation which alters 3D genome conformation, impairing recruitment of the transcriptional repressor EHMT2/G9a/KMT1C, thereby alleviating transcriptional repression of ESR1 in EC. Conclusions In summary, we identify a complex genomic-epigenomic interplay in EC development and progression, altering 3D genome organization to enhance expression of the critical driver ERα.

The risk of developing gastric cancer is increased in patients treated with radiotherapy for Hodgkin lymphoma (HL) or testicular cancer (TC). This study aims to assess if gastric adenocarcinoma after treatment for HL/TC (t-GC) is molecularly different from gastric adenocarcinoma in the general population. Molecular subtyping of 90 t-GCs resulted in 3% EBV, 8% MSI, 36% sCIN and 53% sGS. 3/6 of MSI t-GCs had MLH1 promoter methylation and 2/6 were explained by double somatic mutations in MMR genes. T-GCs were more frequently sGS than p-GCs (53% vs. 38%, p = 0.04). T-GC was more frequently sGS in HL/TC patients diagnosed before 1990, than after 1990 (63% vs. 38%, p = 0.03). T-GCs located in the antrum, an area that receives high irradiation doses, were more frequently sGS (61% vs. 28% in p-GCs, p = 0.02). Our results demonstrate that t-GCs are more frequently of the sGS subtype than p-GCs. An association of t-GC of the sGS subtype with prior anticancer treatment is suggested by the high frequency in HL/TC patients who were treated before 1990, a time period in which HL/TC treatments were more extensive.

PurposeAnthracyclines and trastuzumab can increase the risk of heart failure (HF), but long-term cardiotoxicity data in breast cancer (BC) patients treated at younger ages are limited. Furthermore, it is unknown whether aromatase inhibitors are associated with HF risk.MethodsHF risk was studied in a multicenter cohort of BC survivors treated during 2000–2009, at age < 61 years. Information on treatment and cardiovascular disease incidence was collected through medical records, general practitioners and cardiologists. Analyses included multivariable Cox regression and cumulative incidence curves.ResultsIn total, 10,209 women with a median age at BC diagnosis of 50.3 years and a median follow-up of 8.9 years were enrolled in the study. Anthracycline-based chemotherapy was associated with HF (hazard ratio [HR] 2.18, 95% confidence interval [CI] 1.41–3.39) and risk increased with increasing cumulative anthracycline dose. For trastuzumab, HF risk was highest within the first 2 years after treatment (HR0–2 years: 13.06, 95% CI 5.70–29.92) and decreased thereafter (HR2–4 years: 4.84, 95% CI 1.99–11.75 and HR≥4 years: 0.64, 95% CI 0.23–1.81). The 10-year cumulative incidence of HF was 4.8% (95% CI 3.2–6.8) among patients treated with anthracyclines and trastuzumab. One-third of patients who developed HF after trastuzumab had long-term impaired cardiac function. Patients treated with aromatase inhibitors alone also had higher HF risk (HR 2.18, 95% CI 1.24–3.82) compared to patients not receiving endocrine therapy.ConclusionsOur results stress the importance of considering anthracycline-free regimens in BC patients who need trastuzumab-containing treatment. The association between aromatase inhibitors and HF needs confirmation.