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Simple Summary: This study focuses on Stage IIIA-N2 non-small cell lung cancer (NSCLC), which occurs when lung cancer has spread to lymph nodes in the centre of the chest but not to distant parts of the body. This type of cancer is difficult to treat, and survival rates remain low despite advances in therapy. The research is based on real-world data from Guy's Thoracic Cancer Database and aims to enhance our understanding of patient outcomes and identify important factors that impact survival and disease progression. By examining various treatment strategies, the study aims to offer insights that could help tailor treatment approaches to individual patients. The findings underscore the need for personalised care and the potential benefits of incorporating newer therapeutic options, ultimately leading to better survival outcomes for patients with this challenging form of lung cancer. Background: Stage IIIA-N2 non-small cell lung cancer (NSCLC) poses a significant clinical challenge, with low survival rates despite advances in therapy. The lack of a standardised treatment approach complicates patient management. This study utilises real-world data from Guy's Thoracic Cancer Database to analyse patient outcomes, identify key predictors of overall survival (OS) and disease-free survival (DFS), and address the limitations of randomised controlled trials. Methods: This observational, single-centre, non-randomised study analysed 142 patients diagnosed with clinical and pathological T1/2 N2 NSCLC who received curative treatment from 2015 to 2021. Patients were categorised into three groups: Group A (30 patients) underwent surgery for clinical N2 disease, Group B (54 patients) had unsuspected N2 disease discovered during surgery, and Group C (58 patients) received radical chemoradiation or radiotherapy alone (CRT/RT) for clinical N2 disease. Data on demographics, treatment types, recurrence, and survival rates were analysed. Results: The median OS for the cohort was 31 months, with 2-year and 5-year OS rates of 60% and 30%, respectively. Group A had a median OS of 32 months, Group B 36 months, and Group C 25 months. The median DFS was 18 months overall, with Group A at 16 months, Group B at 22 months, and Group C at 17 months. Significant predictors of OS included ECOG performance status, lymphovascular invasion, and histology. No significant differences in OS were found between treatment groups (p = 0.99). Conclusions: This study highlights the complexity and diversity of Stage IIIA-N2 NSCLC, with no single superior treatment strategy identified. The findings underscore the necessity for personalised treatment approaches and multidisciplinary decision-making. Future research should focus on integrating newer therapeutic modalities and conducting multi-centre trials to refine treatment strategies. Collaboration and ongoing data collection are crucial for improving personalised treatment plans and survival outcomes for Stage IIIA-N2 NSCLC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: We conducted a retrospective, population-based study comparing overall survival (OS) between males and females with neuroendocrine neoplasia (NEN). In total, 14,834 cases of NEN recorded in England's National Cancer Registry and Analysis Service (NCRAS)), were analysed. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Females displayed increased survival irrespective of the stage, morphology or level of deprivation, which was statistically significant in NEN of the lung, pancreas, rectum and stomach (p < 0.001). Stage of tumour mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. Females diagnosed with NEN tend to survive longer than males, and stage at presentation only accounts for part of this effect. Future research in NEN, as well as prognostication and treatment, should consider sex as an important factor. Pre-clinical studies have suggested sex hormone signalling pathways may influence tumorigenesis in neuroendocrine neoplasia (NEN). We conducted a retrospective, population-based study to compare overall survival (OS) between males and females with NEN. A total of 14,834 cases of NEN diagnosed between 2012 and 2018, recorded in England's National Cancer Registry and Analysis Service (NCRAS), were analysed. The primary outcome was OS with 5 years maximum follow-up. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Appendiceal, pulmonary and early-stage NEN were most commonly diagnosed in females; stomach, pancreatic, small intestinal, colonic, rectal and later-stage NEN were more often diagnosed in males. Females displayed increased survival irrespective of the stage, morphology or level of deprivation. On average, they survived 3.62 (95% CI 1.73–5.90) to 10.26 (6.6–14.45) months longer than males; this was statistically significant in NEN of the lung, pancreas, rectum and stomach (p < 0.001). The stage mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. The reasons underlying these differences are not yet understood. Overall, females diagnosed with NEN tend to survive longer than males, and the stage at presentation only partially explains this. Future research, as well as prognostication and treatment, should consider sex as an important factor. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer in young adults spans all ethnic backgrounds and is associated with advanced disease and poor outcomes. Identification of genetic changes that are associated with disease and can subsequently be targeted with specific therapies is associated with improved survival. As such, comprehensive molecular testing is recommended in all advanced young adults with non-small cell lung cancer. (1) Background: Non-small cell lung cancer (NSCLC) in young patients is uncommon. Real-world evidence on the outcomes of these patients is limited. (2) Methods: We conducted a retrospective cohort study of young NSCLC patients, age < 50 years at diagnosis, who were treated between 2011–2020 in South-East-London cancer centres. Clinicopathological characteristics, treatment and outcomes were analysed. (3) Results: Of 248 NSCLC patients, median age was 46 years, 50% (n = 125) female, 58% (n = 145) white, 18% (n = 45) black and 4% (n = 10) Asian ethnicity. Amongst patients with a documented smoking history, 30% (n = 64) were never-smokers. Most patients had adenocarcinoma (77%, n = 191) and presented with metastatic disease (67%, n = 166). Only 31% (n = 76) had treatment with curative intent. In patients who presented or developed metastatic non-squamous NSCLC (n = 179), EGFR mutation status was known in 88% (n = 157) and mutation present in 19% (n = 34), ALK was known in 66% (n = 118) with a translocation in 10% (n = 18), ROS1 status was known in 57% (n = 102) with a translocation in 4% (n = 8), and KRAS status was known in 66% (n = 119) with a mutation in 12% (n = 22). Overall, 76% (n = 152) patients with metastatic NSCLC received first-line systemic anti-cancer therapy. Median overall survival in metastatic NSCLC was 9.0 months (95% CI 6.5–11.6 months), with superior median overall survival in those with a targeted therapy option (28.7 months) compared to those without (6.6 months; p < 0.001). (4) Conclusion: Young patients contribute a significant proportion of those presenting with lung cancer. They present with advanced stage at diagnosis and have a poor prognosis. Identification of a targeted therapy option is associated with improved survival. However, most patients do not have a known genomic driver, which is in part due to limited testing, particularly in the early years of this study period. These findings highlight the particular importance of rapid-turnaround comprehensive genomic profiling in this age group and the need to identify strategies to facilitate earlier diagnosis in young NSCLC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic prostate cancer (mPCa) is one of the most common solid tumors in men and both the disease and the treatments affect patients' quality of life (QoL). Patient-reported Outcome Measurements (PROMs) are important to assess the patient's subjective experience with disease and treatment. Our aim is to appraise, compare, and summarize the psychometric properties of Patient-reported Outcome Measures (PROMs). Our findings can improve patients' care and their quality of life during treatment and the disease path. Introduction: Patient-reported outcome measures (PROMs) represent important endpoints in metastatic prostate cancer (mPCa). However, the clinically valid and accurate measurement of health-related quality of life depends on the psychometric properties of the PROMs considered. Objective: To appraise, compare, and summarize the properties of PROMs in mPCa. Evidence acquisition: We performed a review of PROMs used in RCTs, including patients with mPCa, using Medline in September 2021, according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. This systematic review is part of PIONEER (an IMI2 European network of excellence for big data in PCa). Results: The most frequently used PROMs in RCTs of patients with mPCa were the Functional Assessment for Cancer Therapy—Prostate (FACT-P) (n = 18), the Brief Pain Inventory—Short Form (BPI-SF) (n = 8), and the European Organization for Research and Treatment of Cancer quality of life core 30 (EORTC QLQ-C30) (n = 6). A total of 283 abstracts were screened and 12 full-text studies were evaluated. A total of two, one, and two studies reported the psychometric proprieties of FACT-P, Brief Pain Inventory (BPI), and BPI-SF, respectively. FACT-P and BPI showed a high content validity, while BPI-SF showed a moderate content validity. FACT-P and BPI showed a high internal consistency (summarized by Cronbach's α 0.70–0.95). Conclusions: The use of BPI and FACT-P in mPCa patients is supported by their high content validity and internal consistency. Since BPI is focused on pain assessment, we recommend FACT-P, which provides a broader assessment of QoL and wellbeing, for the clinical evaluation of mPCa patients. However, these considerations have been elaborated on in a very limited number of studies. Patient summary: In this paper, we review the psychometric properties of PROMs used with patients with mPCa to find the questionnaires that best assess patients' QoL, in order to help professionals in their intervention and improve patients' QoL. We recommend the use of BPI and FACT-P for their high content validity and internal consistency despite the limited number of studies considered. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) are drugs which treat cancer by manipulating the immune system. Exercise also influences the immune system and helps to reduce symptoms in people with cancer, particularly fatigue. However, the effect of combining exercise with ICIs has not been well established. We hypothesise that the combined approach will produce beneficial outcomes for people with cancer (such as fewer side effects from ICIs and better killing of cancer cells). To determine the need for, and design of, future studies which address this hypothesis, we first need to understand what previous research has already shown. We aim to identify previous studies which have investigated this topic. Subsequently, by summarising their findings, we aim to communicate the key gaps in current understanding and provide informed recommendations about the direction, and design, of future research addressing the role of exercise during ICI treatment for people with cancer. The impact of using exercise as a non-pharmacological intervention in patients with cancer receiving immune checkpoint inhibitors (ICIs) is not well known. Our objective was to determine the extent of, and identify gaps within, available literature addressing the effect of exercise on (a) oncological outcomes and (b) quality of life (QoL) in patients with cancer receiving ICIs, and (c) the underlying biological mechanisms for such effects. We conducted searches across EMBASE, APA PsycInfo and Ovid MEDLINE(R). Studies were eligible if they addressed at least one aspect of the objective and were available in the English language. Results were synthesised using a narrative approach and subsequently discussed with multidisciplinary stakeholders. As of the final search on 5 April 2022, 11 eligible studies were identified, of which 8 were preclinical and 3 were clinical. Clinical studies only focused on QoL-related outcomes. When studies were grouped by whether they addressed oncological outcomes (n = 7), QoL (n = 5) or biological mechanisms (n = 7), they were found to be heterogeneous in methodology and findings. Additional evidence, particularly in the clinical setting, is required before robust recommendations about whether, and how, to include exercise alongside ICI treatment can be made. [ABSTRACT FROM AUTHOR]

Introduction: Treatment choice for localized prostate cancer is complicated, as each treatment option comes with various pros and cons. It is well established that active surveillance (AS), may be ended with a change to curative treatment at the time of disease progression, but it is less clear whether secondary treatment after initial curative treatment is required. As part of the PIONEER project, we quantified the probabilities of treatment change. Methods: A cohort study based on PRIAS and ERSPC-Rotterdam data was conducted. Patients were followed up for 10 years or until the 31st of December 2017. The primary outcome was the incidence of treatment change following initial treatment (i.e., a change to curative treatment following AS or secondary treatment after initial RP/RT). Results: Over a period of 1 to 5 years after initial treatment, the cumulative incidence of treatment change ranged from 3.8% to 42.8% for AS, from 7.6% to 12.1% for radical prostatectomy (RP) and from no change to 5.3% for radiation therapy (RT). While the possibility of treatment change in AS is known, the numbers within a five-year period were substantial. For RP and RT, the rate of change to secondary treatment was lower, but still non-neglectable, with 5 (10)-year incidences up to 12% (20%) and 5% (16%), respectively. Conclusion: This is one of the first studies comparing the incidence of guideline-recommended treatment changes in men receiving different primary treatments (i.e., AS, RT, or RP) for localized prostate cancer (PCa). [ABSTRACT FROM AUTHOR]

Simple Summary: Several studies published to date have shown inconclusive results in the association between serum bilirubin and risk of site-specific cancer types and overall cancer. Therefore, there is a need to further investigate this association. Data from the large Swedish Apolipoprotein Mortality Risk (AMORIS) cohort study was used. We found that overall high levels of bilirubin had no association with overall cancer risk. However, a positive association was found between melanoma and breast cancer risk. On the other hand, an inverse association was found between high levels of bilirubin and risk of gynecological and lung cancers. Further studies are required to establish if bilirubin can be used as a biomarker for risk assessment and/or as a novel therapeutic target. Bilirubin has strong antioxidant properties that have been hypothesized to be preventive against the development of cancer. Thus, we aimed to investigate the association between serum total bilirubin (STB) and risk of overall and site-specific cancers in the large Swedish Apolipoprotein Mortality Risk (AMORIS) cohort. We also performed a systematic review and meta-analysis for specific cancer types (colorectal, breast and lung). We found no association between high levels of STB and risk of overall cancer. Regarding site-specific cancer, there was an inverse association between increased STB and lung cancer (Hazard Ratio (HR) for the 4th quartile (Q4) vs. Q1: 0.50; 95%CI: 0.44–0.59) and gynecological cancer (HR for Q4 vs. Q1: 0.86; 95%CI: 0.76–0.99). A positive association was found with melanoma (HR for Q4 vs. Q1: 1.25; 95%CI: 1.06–1.47) and breast cancer (HR for Q4 vs. Q1: 1.13; 95%CI: 1.01–1.25) risk. The meta-analysis showed an inverse association between high levels of STB and risk of lung cancer (Relative risk (RR): 0.69; 95%CI: 0.55–0.86). No associations were seen for colorectal and breast cancer risk. Further studies are required to establish if bilirubin can be used as a biomarker for risk assessment and/or as a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells (CTCs) can be found in the bloodstream in men with advanced prostate cancer. Blood platelets, which normally help the blood to clot, may help the cancer cells to spread throughout the body by preventing the body's immune system from finding and destroying them while they are in the bloodstream. Blood samples were taken from men with prostate cancer who were involved in the ExPeCT clinical trial, some of whom were taking part in a regular exercise programme. The numbers of CTCs, platelets and immune system cells were counted and compared. Blood samples with more CTCs had higher numbers of platelets and higher numbers of some types of immune system cells. Some differences were also found in men involved in the exercise programme. This study helps to show that CTCs numbers are related to platelet and immune cell numbers in the blood. Interactions between circulating tumour cells (CTCs) and platelets are thought to inhibit natural killer(NK)-cell-induced lysis. We attempted to correlate CTC numbers in men with advanced prostate cancer with platelet counts and circulating lymphocyte numbers. Sixty-one ExPeCT trial participants, divided into overweight/obese and normal weight groups on the basis of a BMI ≥ 25 or <25, were randomized to participate or not in a six-month exercise programme. Blood samples at randomization, and at three and six months, were subjected to ScreenCell filtration, circulating platelet counts were obtained, and flow cytometry was performed on a subset of samples (n = 29). CTC count positively correlated with absolute total lymphocyte count (r2 = 0.1709, p = 0.0258) and NK-cell count (r2 = 0.49, p < 0.0001). There was also a positive correlation between platelet count and CTC count (r2 = 0.094, p = 0.0001). Correlation was also demonstrated within the overweight/obese group (n = 123, p < 0.0001), the non-exercise group (n = 79, p = 0.001) and blood draw samples lacking platelet cloaking (n = 128, p < 0.0001). By flow cytometry, blood samples from the exercise group (n = 15) had a higher proportion of CD3+ T-lymphocytes (p = 0.0003) and lower proportions of B-lymphocytes (p = 0.0264) and NK-cells (p = 0.015) than the non-exercise group (n = 14). These findings suggest that CTCs engage in complex interactions with the coagulation cascade and innate immune system during intravascular transit, and they present an attractive target for directed therapy at a vulnerable stage in metastasis. [ABSTRACT FROM AUTHOR]

Simple Summary: Although COVID-19 vaccine side effects are generally well tolerated, information on cancer patients is lacking due to their exclusion from original clinical trials. The aim of our study was to report on the safety of COVID-19 vaccines in our cancer patients. Data on vaccine side effects from our London cancer center was collected from 8 December 2020 to 28 February 2021. Reassuringly, we observed that cancer patients tolerated the first dose of COVID-19 vaccine very well with minimal serious side effects. Similar to the vaccine clinical trials, the most common side effects were having a sore arm, tiredness, and headaches. Emergency approval of vaccines against COVID-19 provides an opportunity for us to return to pre-pandemic oncology care. However, safety data in cancer patients is lacking due to their exclusion from most phase III trials. We included all patients aged less than 65 years who received a COVID-19 vaccine from 8 December 2020 to 28 February 2021 at our London tertiary oncology centre. Solicited and unsolicited vaccine-related adverse events (VRAEs) were collected using telephone or face-to-face consultation. Within the study period, 373 patients received their first dose of vaccine: Pfizer/BioNTech (75.1%), Oxford/AstraZeneca (23.6%), Moderna (0.3%), and unknown (1.1%). Median follow-up was 25 days (5–85). Median age was 56 years (19–65). Of the patients, 94.9% had a solid malignancy and 76.7% were stage 3–4. The most common cancers were breast (34.0%), lung (13.4%), colorectal (10.2%), and gynaecological (10.2%). Of the patients, 88.5% were receiving anti-cancer treatment (36.2% parenteral chemotherapy and 15.3% immunotherapy), 76.1% developed any grade VRAE of which 2.1% were grade 3. No grade 4/5 or anaphylaxis were observed. The most common VRAEs within 7 days post-vaccination were sore arm (61.7%), fatigue (18.2%), and headaches (12.1%). Most common grade 3 VRAE was fatigue (1.1%). Our results demonstrate that COVID-19 vaccines in oncology patients have mild reactogenicity. [ABSTRACT FROM AUTHOR]

Simple Summary: Around 10–15% of breast cancer diagnoses are invasive lobular cancers (ILC), and they are currently treated in a similar way to the more common invasive ductal cancer (IDC), although they display different characteristics. The main objective of this study was to identify any differences in outcome following chemotherapy treatment between ILC and oestrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2−) IDC. Results from the analysis show worse survival in patients with ER+HER2− ILC after chemotherapy compared to ER+HER2− IDC, even after correcting for tumour size, grade, age, and nodal involvement at presentation, suggesting a worse response to chemotherapy in ILC. Thus, recommendations for chemotherapy treatment should be considered separately for the two subtypes. However, this association should be studied in a larger population to confirm this finding. Invasive lobular breast cancer (ILC) accounts for 10–15% of breast cancers and has distinct characteristics compared with the more common invasive ductal carcinoma (IDC). Studies have shown that ILC may be less sensitive to chemotherapy than IDC, with lower rates of complete pathological response after neo-adjuvant chemotherapy, but it is not clear how this affects long-term survival. Patients at Guy's and St Thomas' NHS Foundation Trust between 1975 and 2016 diagnosed with ER+ IDC or ER+ ILC were eligible for inclusion. Kaplan–Meier plots and Cox proportional-hazards regression models were used for analysis. There was no difference in overall survival comparing ER+ ILC to ER+ IDC (OR: 0.94, 95% CI: 0.83, 1.04) with a median follow-up time of 8.3 years compared to 8.4 years in IDC. However, ER+HER2− ILC had worse survival compared to ER+HER2− IDC in those that received chemotherapy (OR: 1.46, 95% CI: 1.06, 2.01). Here, median follow-up time was 7.0 years in ILC compared to 8.1 years in IDC. These results indicate worse overall survival after chemotherapy (neo-adjuvant and adjuvant) in ILC compared to ER+HER2− IDC even when correcting for tumour grade, age, size, and nodal involvement, but validation is needed in a larger study population. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence of a disease during a life span. The development of an exposome approach for PCa has the potential to discover new disease-associated factors to better understand the carcinogenesis of PCa and help with early detection strategies. Our systematic review of the literature identified several exposome factors that have been associated with PCa alone and in combination with other exposures. A potential inflammatory signature has been observed among the interaction of several exposures (i.e., smoking, alcohol consumption, diabetes mellitus, obesity, and inflammatory markers) that further increases the incidence and progression of PCa. A large number of exposures have been identified such as genetic, hormonal, microorganism infections and immune responses that warrant further investigation. Future early detection strategies should utilize this information to assess individuals' risk for PCa. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the outcome of cancer patients undergoing systemic anti-cancer treatment (SACT) at our centre to help inform future clinical decision-making around SACT during the COVID-19 pandemic., Methods: Patients receiving at least one episode of SACT for solid tumours at Guy's Cancer Centre between 1 March and 31 May 2020 and the same period in 2019 were included in the study. Data were collected on demographics, tumour type/stage, treatment type (chemotherapy, immunotherapy, biological-targeted) and SARS-CoV2 infection., Results: A total of 2120 patients received SACT in 2020, compared to 2449 in 2019 (13% decrease). From 2019 to 2020, there was an increase in stage IV disease (62% vs. 72%), decrease in chemotherapy (42% vs. 34%), increase in immunotherapy (6% vs. 10%), but similar rates of biologically targeted treatments (37% vs. 38%). There was a significant increase in 1st and 2nd line treatments in 2020 (68% vs. 81%; p < 0.0001) and reduction in 3rd and subsequent lines (26% vs. 15%; p = 0.004) compared to 2019. Of the 2020 cohort, 2% patients developed SARS-CoV2 infections., Conclusions: These real-world data from a tertiary Cancer Centre suggest that despite the challenges faced due to the COVID-19 pandemic, SACT was able to be continued without any significant effects on the mortality of solid-tumour patients. There was a low rate (2%) of SARS-CoV-2 infection which is comparable to the 1.4%-point prevalence in our total cancer population.

Very few studies investigating COVID-19 in cancer patients have included cancer patients as controls. We aimed to identify factors associated with the risk of testing positive for SARS CoV2 infection in a cohort of cancer patients. We analyzed data from all cancer patients swabbed for COVID-19 between 1 st March and 31 st July 2020 at Guy's Cancer Centre. We conducted logistic regression analyses to identify which factors were associated with a positive COVID-19 test. Results: Of the 2152 patients tested for COVID-19, 190 (9%) tested positive. Male sex, black ethnicity, and hematological cancer type were positively associated with risk of COVID-19 (OR = 1.85, 95%CI:1.37-2.51; OR = 1.93, 95%CI:1.31-2.84; OR = 2.29, 95%CI:1.45-3.62, respectively) as compared to females, white ethnicity, or solid cancer type, respectively. Male, Asian ethnicity, and hematological cancer type were associated with an increased risk of severe COVID-19 (OR = 3.12, 95%CI:1.58-6.14; OR = 2.97, 95%CI:1.00-8.93; OR = 2.43, 95%CI:1.00-5.90, respectively). This study is one of the first to compare the risk of COVID-19 incidence and severity in cancer patients when including cancer patients as controls. Results from this study have echoed those of previous reports, that patients who are male, of black or Asian ethnicity, or with a hematological malignancy are at an increased risk of COVID-19.

The SARS-CoV-2 (COVID-19) pandemic is having a large effect on the management of cancer patients. This study reports on the approach and outcomes of cancer patients receiving radical surgery with curative intent between March and September 2020 (in comparison to 2019) in the European Institute of Oncology, IRCCS (IEO) in Milan and the South East London Cancer Alliance (SELCA). Both institutions implemented a COVID-19 minimal pathway where patients were required to self-isolate prior to admission and were swabbed for COVID-19 within 72 h of surgery. Positive patients had surgery deferred until a negative swab. At IEO, radical surgeries declined by 6% as compared to the same period in 2019 ( n = 1477 vs. 1560, respectively). Readmissions were required for 3% ( n = 41), and <1% ( n = 9) developed COVID-19, of which only one had severe disease and died. At SELCA, radical surgeries declined by 34% ( n = 1553 vs. 2336). Readmissions were required for 11% ( n = 36), <1% ( n = 7) developed COVID-19, and none died from it. Whilst a decline in number of surgeries was observed in both centres, the implemented COVID-19 minimal pathways have shown to be safe for cancer patients requiring radical treatment, with limited complications and almost no COVID-19 infections.

To investigate the association between serum calcium and risk of breast cancer using a large cohort and a systematic review with meta-analysis. From the Swedish Apolipoprotein Mortality Risk (AMORIS) Study we included 229,674 women who had baseline measurements of serum total calcium and albumin. Multivariable Cox regression was used to assess the association between total and albumin-corrected calcium and breast cancer risk. For the systematic review, an electronic search of MEDLINE and EMBASE databases was performed to identify other prospective cohorts assessing the relationship between serum calcium and breast cancer risk. We pooled the results of our AMORIS cohort with other eligible studies in a meta-analysis using a random effects model. I² test was used to assess heterogeneity. In the AMORIS study, 10,863 women were diagnosed with breast cancer (mean follow-up: 19 years). We found an inverse association between total serum calcium and breast cancer when comparing the fourth quartile to the first quartile (HR: 0.94, 95% CI: 0.88-0.99, p value for trend 0.04) and similar results using albumin-corrected calcium. In the systematic review, we identified another two prospective cohorts evaluating pre-diagnostic serum total calcium and breast cancer. Combining these studies and our findings in AMORIS in a meta-analysis showed a protective effect of serum calcium against breast cancer, with a summary RR of 0.80 (95% CI: 0.66-0.97). No substantial heterogeneity was observed. Our findings in AMORIS and the meta-analysis support an inverse association between serum calcium and breast cancer risk, which warrants mechanistic investigations., Competing Interests: Niklas Hammar is employed by AstraZeneca. However, the views expressed in this study are his own and not those of AstraZeneca’s. No medical writer was involved in the study or manuscript preparation.