Showing papers in "International Journal of Cancer in 2022"
TL;DR: Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option.
Abstract: Optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is controversial, especially in the context of potential benefit of combining PD‐1 blockade with neoadjuvant therapy. This phase 2 study aimed to assess neoadjuvant camrelizumab plus chemotherapy in this population. Patients (clinical stage II‐IVA) received two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab‐paclitaxel (260 mg/m2 in total on day 1 and day 8) and cisplatin (75 mg/m2 in total on days 1‐3) of each 21‐day cycle. Surgery was performed approximately 6 weeks after completion of NIC. Primary endpoint was complete pathologic response (CPR) rate in primary tumor. Secondary endpoints were objective response rate (ORR) per RECIST v1.1, 2‐year progression‐free survival (PFS) rate after surgery, PFS, overall survival (OS) and safety during NIC and perioperative period. Between 17 January 2020 and 8 December 2020, 56 patients were enrolled, and 51 received esophagectomy. Data cutoff date was 25 August 2021. The CPR rate was 35.3% (95% CI, 21.7%‐48.9%). NIC had an ORR of 66.7% (95% CI, 40.0%‐70.4%) and treatment‐related adverse events (TRAEs) of low severity (grade 1‐2, 75.0%; grade 3, 10.7%; grade 4‐5, no). No perioperative mortality occurred. Three (5.9%) patients had tumor recurrence and one (2.0%) patient died. The 2‐year PFS rate, median PFS and median OS had not been reached yet. Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option. Study is ongoing for long‐term survival analyses.
46 citations
TL;DR: The study highlights the disproportionate current and future burden of ovarian cancer in countries with lower HDI levels, calling for global action to reduce the burden and inequality of ovarian cancer in access to quality cancer care and treatment.
Abstract: Ovarian cancer remains to have relatively poor prognosis particularly in low‐resourced settings. It is therefore important to continually examine the burden of ovarian cancer to identify areas of disparities. Our study aims to provide an overview of the global burden of ovarian cancer using the GLOBOCAN 2020 estimates by country, world region, and Human Development Index (HDI) levels, as well as the predicted future burden by the year 2040 by HDI. Age‐standardized incidence and mortality rates for ovarian cancer in 185 countries were calculated by country, world region, and for the four‐tier HDI. The number of new cases and deaths were projected for the year 2040 based on demographic projections by HDI category. Approximately 314 000 new ovarian cancer cases and 207 000 deaths occurred in 2020. There were marked geographic variations in incidence rates, with the highest rates observed in European countries with very high HDI and low rates were found in African countries within the lowest HDI group. Comparable mortality rates were observed across the four‐tier HDI. Relative to 2020 estimates, our projection for 2040 indicates approximately 96% and 100% increase in new ovarian cancer cases and deaths, respectively, among low HDI countries compared to 19% and 28% in very high HDI countries. Our study highlights the disproportionate current and future burden of ovarian cancer in countries with lower HDI levels, calling for global action to reduce the burden and inequality of ovarian cancer in access to quality cancer care and treatment.
38 citations
TL;DR: A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group.
Abstract: Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long‐term hormone therapy for prostate cancer. This long‐term analysis in metastatic patients was planned for 3 years after the first results. Standard‐of‐care (SOC) was androgen deprivation therapy. The comparison randomised patients 1:1 to SOC‐alone with or without daily abiraterone acetate 1000 mg + prednisolone 5 mg (SOC + AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards and flexible parametric models, accounting for baseline stratification factors. One thousand and three patients were contemporaneously randomised (November 2011 to January 2014): median age 67 years; 94% newly‐diagnosed; metastatic disease risk group: 48% high, 44% low, 8% unassessable; median PSA 97 ng/mL. At 6.1 years median follow‐up, 329 SOC‐alone deaths (118 low‐risk, 178 high‐risk) and 244 SOC + AAP deaths (75 low‐risk, 145 high‐risk) were reported. Adjusted HR = 0.60 (95% CI: 0.50‐0.71; P = 0.31 × 10−9) favoured SOC + AAP, with 5‐years survival improved from 41% SOC‐alone to 60% SOC + AAP. This was similar in low‐risk (HR = 0.55; 95% CI: 0.41‐0.76) and high‐risk (HR = 0.54; 95% CI: 0.43‐0.69) patients. Median and current maximum time on SOC + AAP was 2.4 and 8.1 years. Toxicity at 4 years postrandomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group.
23 citations
TL;DR: In this paper , a systematic review and meta-analysis of the diagnostic accuracy of anal cancer screening tests in different populations with elevated risk for anal cancer was performed, and the prevalence of AIN2+ was estimated.
Abstract: To inform optimal approaches for detecting anal precancers, we performed a systematic review and meta‐analysis of the diagnostic accuracy of anal cancer screening tests in different populations with elevated risk for anal cancer. We conducted a literature search of studies evaluating tests for anal precancer and cancer (anal intraepithelial neoplasia grade 2 or worse, AIN2+) published between January 1, 1997 to September 30, 2021 in PubMed and Embase. Titles and abstracts were screened for inclusion and included articles underwent full‐text review, data abstraction and quality assessment. We estimated the prevalence of AIN2+ and calculated summary estimates and 95% confidence intervals (CI) of test positivity, sensitivity and specificity and predictive values of various testing strategies, overall and among population subgroups. A total of 39 articles were included. The prevalence of AIN2+ was 20% (95% CI, 17‐29%), and ranged from 22% in men who have sex with men (MSM) living with HIV to 13% in women and 12% in MSM without HIV. The sensitivity and specificity of cytology and HPV testing were 81% and 62% and 92% and 42%, respectively, and 93% and 33%, respectively for cytology and HPV co‐testing. AIN2+ risks were similar among those testing positive for cytology, HPV, or co‐testing. Limited data on other biomarkers (HPV E6/E7 mRNA and p16/Ki‐67 dual stain), suggested higher specificity, but lower sensitivity compared with anal cytology and HPV. Our findings provide important evidence for the development of clinical guidelines using anal cytology and HPV testing for anal cancer screening.
23 citations
TL;DR: A higher mortality burden in countries undergoing economic transitions is indicated and the need for more equitable access to testicular cancer diagnosis and treatment globally is reinforced.
Abstract: With 74 500 new cases worldwide in 2020, testicular cancer ranks as the 20th leading cancer type, but is the most common cancer in young men of European ancestry. While testicular cancer incidence has been rising in many populations, mortality trends, at least those in high‐income settings, have been in decline since the 1970s following the introduction of platinum‐based chemotherapy. To examine current incidence and mortality patterns, we extracted the new cases of, and deaths from cancers of the testis from the GLOBOCAN 2020 database. In 2020, testicular cancer was the most common cancer in men aged 15 to 44 in 62 countries worldwide. Incidence rates were highest in West‐, North‐ and South‐Europe and Oceania (age‐standardised rate, ASR ≥7/100 000), followed by North America (5.6/100 000 and lowest (<2/100 000) in Asia and Africa. The mortality rates were highest in Central and South America (0.84 and 0.54 per 100 000, respectively), followed by Eastern and Southern Europe, and Western and Southern Africa. The lowest mortality rates were in Northern Europe, Northern Africa and Eastern Asia (0.16, 0.14, 0.9 per 100 000, respectively). At the country level, incidence rates varied over 100‐fold, from 10/100 000 in Norway, Slovenia, Denmark and Germany to ≤0.10/100 000 in Gambia, Guinea, Liberia, Lesotho. Mortality rates were highest in Fiji, Argentina and Mexico. Our results indicate a higher mortality burden in countries undergoing economic transitions and reinforce the need for more equitable access to testicular cancer diagnosis and treatment globally.
21 citations
TL;DR: The method has the potential to enter routine diagnostics as a gold standard for cytogenetic diagnostics widely superseding FISH and serve as a tool to identify genetic regions of interest and future research regarding tumor biology.
Abstract: Cytogenetic diagnostics play a crucial role in risk stratification and classification of myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), thus influencing treatment decisions. Optical genome mapping (OGM) is a novel whole genome method for the detection of cytogenetic abnormalities. Our study assessed the applicability and practicality of OGM as diagnostic tool in AML and MDS patients. In total, 27 patients with AML or MDS underwent routine diagnostics including classical karyotyping and fluorescence in situ hybridization (FISH) or real‐time PCR analysis wherever indicated as well as OGM following a recently established workflow. Methods were compared regarding concordance and content of information. In 93%, OGM was concordant to classical karyotyping and a total of 61 additional variants in a predefined myeloid gene‐set could be detected. In 67% of samples the karyotype could be redefined by OGM. OGM offers a whole genome approach to cytogenetic diagnostics in AML and MDS with a high concordance to classical cytogenetics. The method has the potential to enter routine diagnostics as a gold standard for cytogenetic diagnostics widely superseding FISH. Furthermore, OGM can serve as a tool to identify genetic regions of interest and future research regarding tumor biology.
20 citations
TL;DR: In this paper, a combination of traditional clinical criteria and molecular techniques, including MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1 promoter methylation testing and gene sequencing, were used for screening, diagnosis, surveillance, prevention and treatment of Lynch syndrome associated endometrial cancer (LS-EC).
Abstract: Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes. LS-associated endometrial cancer (LS-EC) is the most common extraintestinal sentinel cancer caused by germline PVs in MMR genes, including MLH1, MSH2, MSH6 and PMS2. The clinicopathologic features of LS-EC include early age of onset, lower body mass index (BMI), endometrioid carcinoma and lower uterine segment involvement. There has been significant progress in screening, diagnosis, surveillance, prevention and treatment of LS-EC. Many studies support universal screening for LS among patients with EC. Screening mainly involves a combination of traditional clinical criteria and molecular techniques, including MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1 promoter methylation testing and gene sequencing. The effectiveness of endometrial biopsy and transvaginal ultrasound (TVS) for clinical monitoring of asymptomatic women with LS are uncertain yet. Preventive strategies include hysterectomy and bilateral salpingo-oophorectomy (BSO) as well as chemoprophylaxis using exogenous progestin or aspirin. Recent research has revealed the benefits of immunotherapy for LS-EC. The NCCN guidelines recommend pembrolizumab and nivolumab for treating patients with advanced or recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) EC.
20 citations
TL;DR: A meta‐analysis of test agreement/concordance between human papillomavirus (HPV) testing in self‐col collected vs clinician‐collected samples in 26 studies updating a previous meta‐ analysis on accuracy for cervical precancer suggested higher overall agreement for target amplification‐based DNA assays.
Abstract: We conducted a meta‐analysis of test agreement/concordance between human papillomavirus (HPV) testing in self‐collected vs clinician‐collected samples in 26 studies (10 071 participants) updating a previous meta‐analysis on accuracy for cervical precancer. Pooled overall agreement was 88.7% (95% CI: 86.3%‐90.9%), positive agreement was 84.6% (95% CI: 79.9%‐88.7%), negative agreement was 91.7% (95% CI: 89.1%‐94.0%) and kappa was 0.72 (95% CI: 0.66‐0.78). Subgroup meta‐analyses suggested higher overall agreement for target amplification‐based DNA assays (90.4%) compared to signal amplification‐based DNA assays (86.7%; P = .175) or RNA assays (82.3%; P < .001). HPV test agreement/concordance targets may provide criteria to extend existing validations toward alternative sampling approaches and devices/storage media.
17 citations
TL;DR: This is the first report that ctHPV16 DNA is detectable at least several years before diagnosis of HPV16‐positive HNSCC for a subset of patients.
Abstract: Human papillomavirus (HPV), most commonly HPV16, causes a growing subset of head and neck squamous cell carcinomas (HNSCCs), including the overwhelming majority of oropharynx squamous cell carcinomas in many developed countries. Circulating biomarkers for HPV‐positive HNSCC may allow for earlier diagnosis, with potential to decrease morbidity and mortality. This case‐control study evaluated whether circulating tumor HPV DNA (ctHPVDNA) is detectable in prediagnostic plasma from individuals later diagnosed with HPV‐positive HNSCC. Cases were participants in a hospital‐based research biobank with archived plasma collected ≥6 months before HNSCC diagnosis, and available archival tumor tissue for HPV testing. Controls were biobank participants without cancer or HPV‐related diagnoses, matched 10:1 to cases by sex, race, age and year of plasma collection. HPV DNA was detected in plasma and tumor tissue using a previously validated digital droplet PCR‐based assay that quantifies tumor‐tissue‐modified viral (TTMV) HPV DNA. Twelve HNSCC patients with median age of 68.5 years (range, 51‐87 years) were included. Ten (83.3%) had HPV16 DNA‐positive tumors. ctHPV16DNA was detected in prediagnostic plasma from 3 of 10 (30%) patients with HPV16‐positive tumors, including 3 of 7 (43%) patients with HPV16‐positive oropharynx tumors. The timing of the plasma collection was 19, 34 and 43 months before cancer diagnosis. None of the 100 matched controls had detectable ctHPV16DNA. This is the first report that ctHPV16 DNA is detectable at least several years before diagnosis of HPV16‐positive HNSCC for a subset of patients. Further investigation of ctHPV16DNA as a biomarker for early diagnosis of HPV16‐positive HNSCC is warranted.
16 citations
TL;DR: Inverse association between CDAI and CRC risk was more apparent in women or those without a history of diabetes, without family history of CRC, never smokers or overweight/obese individuals, suggesting that food‐based antioxidants may be beneficial for reducing the risk of CRC in the general population.
Abstract: Colorectal cancer (CRC) is a major contributor to cancer death globally. Several studies showed some protections by certain individual dietary antioxidants against CRC development. Epidemiologic data on the composite dietary antioxidant index (CDAI) in relation to CRC risk are sparse. Using the Singapore Chinese Health Study, an ongoing prospective cohort consisting of 61 321 cancer‐free participants aged 45 to 74 years at baseline, a food‐based CDAI was calculated according to a previously established and validated method that included six food‐sourced antioxidants including vitamins A, C and E, manganese, selenium and zinc. Cox proportional hazard regression method was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for CRC associated with various levels of CDAI with adjustment for multiple potential confounders. After an average of 17.5 years of follow‐up, 2140 participants developed CRC. HRs (95% CIs) of CRC for quartiles 2, 3 and 4 of CDAI were 0.94 (0.83‐1.07), 0.86 (0.75‐1.00) and 0.80 (0.66‐0.98), respectively, compared to the lowest quartile (Ptrend = .02). This inverse association between CDAI and CRC risk was more apparent in women or those without a history of diabetes, without family history of CRC, never smokers or overweight/obese individuals. However, none of the heterogeneity tests for the CDAI‐CRC risk association reached statistical significance. Our findings suggest that food‐based antioxidants may be beneficial for reducing the risk of CRC in the general population.
15 citations
TL;DR: Significant increases in two butyrate‐producing bacteria, Agathobacter M104/1 and Blautia SR1/5 expression were associated with PFS according to their presence or absence in basal fecal samples, and could be potential biomarkers of outcome in mCRC, and NSCLC patients treated with cetuximab + avelumab.
Abstract: Gut microbiota is involved in immune modulation and immune checkpoint inhibitors (ICIs) efficacy. Single‐arm phase II CAVE‐mCRC and CAVE‐LUNG clinical trials investigated cetuximab + avelumab combination in RAS wild‐type (WT) metastatic colorectal cancer (mCRC) and chemo‐refractory nonsmall cell lung cancer (NSCLC) patients, respectively. A comprehensive gut microbiota genetic analysis was done in basal fecal samples of 14 patients from CAVE‐mCRC trial with circulating tumor DNA (ctDNA) RAS/BRAF WT and microsatellite stable (MSS) disease. Results were validated in a cohort of 10 patients from CAVE‐Lung trial. 16S rRNA sequencing revealed 23 027 bacteria species in basal fecal samples of 14 patients from CAVE‐mCRC trial. In five long‐term responding patients (progression‐free survival [PFS], 9‐24 months) significant increases in two butyrate‐producing bacteria, Agathobacter M104/1 (P = .018) and Blautia SR1/5 (P = .023) were found compared to nine patients with shorter PFS (2‐6 months). A significantly better PFS was also observed according to the presence or absence of these species in basal fecal samples. For Agathobacter M104/1, median PFS (mPFS) was 13.5 months (95% confidence interval [CI], 6.5‐20.5 months) vs 4.6 months (95% CI, 1.8‐7.4 months); P = .006. For Blautia SR1/5, mPFS was 5.9 months (95% CI, 2.2‐9.7 months) vs 3.6 months (95% CI, 3.3‐4.0 months); P = .021. Similarly, in CAVE‐Lung validation cohort, Agathobacter M104/1 and Blautia SR1/5 expression were associated with PFS according to their presence or absence in basal fecal samples. Agathobacter and Blautia species could be potential biomarkers of outcome in mCRC, and NSCLC patients treated with cetuximab + avelumab. These findings deserve further investigation.
TL;DR: Whether the COVID‐19 pandemic aggravated health care disparities of cancer outpatients related to their SES and analyzed patient data of the largest university center providing services for patients with hematologic and oncologic disorders in Austria from 2018 to 2021 is investigated.
Abstract: Patients with low socioeconomic status (SES) are among the most underserved groups of people regarding cancer care. Analyzing the impact of the coronavirus‐induced disease 2019 (COVID‐19) pandemic on health care disparities and calling attention to inequalities in cancer care is crucial to justify and initiate adequate countermeasures. We aimed to determine whether the COVID‐19 pandemic aggravated health care disparities of cancer outpatients related to their SES and analyzed patient data of the largest university center providing services for patients with hematologic and oncologic disorders in Austria from 2018 to 2021. SES was assessed using three indicators: monthly net household income, level of education and occupational prestige. In total, 1217 cancer outpatients (51.1% female) with a mean age of 59.4 years (SD = 14.2) participated. In the first year of the pandemic, the relative proportion of individuals with low income, low education level and low occupational prestige seeking cancer care at our outpatient center decreased significantly (P ≤ .015). The strongest indicator was income, with a consistent effect throughout the first pandemic year. Countermeasures and specific interventions to support cancer patients with low SES in their access to health care should be initiated and prioritized.
TL;DR: Postoperative ctDNA status is strongly associated with detection of minimal residual disease and early detection of relapse, and can potentially contribute to clinical decision‐making in case of indeterminate CT findings, reducing time‐to‐intervention.
Abstract: The recurrence rate of colorectal liver metastases (CRLM) patients treated with curative intent is above 50%. Standard of care surveillance includes intensive computed tomographic (CT) imaging as well as carcinoembryonic antigen (CEA) measurements. Nonetheless, relapse detection often happens too late to resume curative treatment. This longitudinal cohort study enrolled 115 patients with plasma samples (N = 439) prospectively collected before surgery, postoperatively at day 30 and every third month for up to 3 years. Droplet digital PCR (ddPCR) was used to monitor serial plasma samples for somatic mutations. Assessment of ctDNA status either immediately after surgery, or serially during surveillance, stratified the patients into groups of high and low recurrence risk (hazard ratio [HR], 7.6; 95% CI, 3.0‐19.7; P < .0001; and HR, 4.3; 95% CI, 2.3‐8.1; P < .0001, respectively). The positive predictive value (PPV) of ctDNA was 100% in all postoperative analyses. In multivariable analyses, postoperative ctDNA status was the only consistently significant risk marker associated with relapse (P < .0001). Indeterminate CT findings were observed for 30.8% (21/68) of patients. All patients (9/21) that were ctDNA positive at the time of the indeterminate CT scan later relapsed, contrasting 42.6% (5/12) of those ctDNA negative (P = .0046). Recurrence diagnoses in patients with indeterminate CT findings were delayed (median 2.8 months, P < .0001). ctDNA status is strongly associated with detection of minimal residual disease and early detection of relapse. Furthermore, ctDNA status can potentially contribute to clinical decision‐making in case of indeterminate CT findings, reducing time‐to‐intervention.
TL;DR: The clinical aspects of ICI‐associated myocarditis are summarized, highlighting its radiological aspects and a novel algorithm for the use of CMR is proposed.
Abstract: Immune checkpoint inhibitor (ICI)‐induced cardiotoxicity is a rare immune‐related adverse event (irAE) characterized by a high mortality rate. From a pathological point of view, this condition can result from a series of causes, including binding of ICIs to target molecules on nonlymphocytic cells, cross‐reaction of T lymphocytes against tumor antigens with off‐target tissues, generation of autoantibodies and production of proinflammatory cytokines. The diagnosis of ICI‐induced cardiotoxicity can be challenging, and cardiac magnetic resonance (CMR) represents the diagnostic tool of choice in clinically stable patients with suspected myocarditis. CMR is gaining a central role in diagnosis and monitoring of cardiovascular damage in cancer patients, and it is entering international cardiology and oncology guidelines. In this narrative review, we summarized the clinical aspects of ICI‐associated myocarditis, highlighting its radiological aspects and proposing a novel algorithm for the use of CMR.
TL;DR: There is an urgent need to develop PRS specific for other ethnicities, in order to widen access of this technology, and SNP‐PRS that has been normalized based on White European ethnicity for breast cancer should not be used to predict risk in women of other Ethnicities.
Abstract: Polygenic risk scores (PRS) for disease risk stratification show great promise for application in general populations, but most are based on data from individuals of white European origin. We assessed two well validated PRS (SNP18, SNP143) in the Predicting-Risk-of-Cancer-At-Screening (PROCAS) study in North-West England for breast cancer prediction based on ethnicity. Overall, 9475 women without breast cancer at study entry, including 645 who subsequently developed invasive breast cancer or ductal carcinoma in situ provided DNA. All were genotyped for SNP18 and a subset of 1868 controls were genotyped for SNP143. For white Europeans both PRS discriminated well between individuals with and without cancer. For n=395 Black (n=112), Asian (n=119), mixed (n=44) or Jewish (n=120) women without cancer both PRS overestimated breast cancer risk, being most marked for women of Black and Jewish origin (p<0.001). SNP143 resulted in a potential mean 40% breast cancer risk overestimation in the combined group of non-white/non-European origin. SNP-PRS that has been normalized based on white European ethnicity for breast cancer should not be used to predict risk in women of other ethnicities. There is an urgent need to develop PRS specific for other ethnicities, in order to widen access of this technology. This article is protected by copyright. All rights reserved.
TL;DR: Durvalumab showed promising clinical activity with encouraging response rates and satisfactory survival outcomes in mCRC patients with MSI‐H/dMMR or POLE EDM, and in patients with POLE‐mutated mC CRC, clinical response to durvalumrab may be restricted to those with EDM.
Abstract: The aim of our study is to evaluate the clinical efficacy of durvalumab in patients with microsatellite instability‐high/mismatch repair‐deficient (MSI‐H/dMMR) or polymerase epsilon (POLE)‐mutated metastatic or unresectable colorectal cancer (mCRC) who had disease progression after standard chemotherapy. This prospective, open‐label, multicenter, phase II study enrolled patients with mCRC harboring MSI‐H/dMMR or POLE mutations treated with at least one prior line of therapy. The participants received durvalumab (1500 mg) every 4 weeks intravenously. The primary endpoint was the objective response rate (ORR). Of the 33 patients, 30 had MSI‐H/dMMR and 3 had POLE‐mutated microsatellite stable (MSS) CRC. With a median follow‐up duration of 11.2 months (95% confidence interval [CI]: 7.3‐15.0), the ORR was 42.4% (95% CI: 25.5‐60.8). Among three patients with POLE‐mutated CRC, one patient who had an exonuclease domain mutation (EDM) achieved an objective response, but the others with mutations in the non‐exonuclease domain had progressive disease. Overall, the median duration of response was not reached and 85.7% of the responses were ongoing at data cutoff. The progression‐free survival rate of 12 months was 58.2% (95% CI: 39.0‐73.1) and the 12‐month overall survival rate was 68.3% (95% CI: 48.8‐81.7). Grade 3 treatment‐related adverse events occurred in 36.4% of the patients and were manageable. In conclusion, durvalumab showed promising clinical activity with encouraging response rates and satisfactory survival outcomes in mCRC patients with MSI‐H/dMMR or POLE EDM. In patients with POLE‐mutated mCRC, clinical response to durvalumab may be restricted to those with EDM.
TL;DR: SCCA burden by HIV status can inform SCCA prevention programs (through HPV vaccination, screening, and HIV control) and help raise awareness to combat the disease.
Abstract: Squamous cell carcinoma of the anus (SCCA) is caused by HPV, and is elevated in persons living with HIV (PLWHIV). We aimed to estimate sex‐ and HIV‐stratified SCCA burden at a country, regional and global level. Using anal cancer incidence estimates from 185 countries available through GLOBOCAN 2020, and region/country‐specific proportions of SCCA vs non‐SCCA from the Cancer Incidence in Five Continents (CI5) Volume XI database, we estimated country‐ and sex‐specific SCCA incidence. Proportions of SCCA diagnosed in PLWHIV, and attributable to HIV, were calculated using estimates of HIV prevalence (UNAIDS 2019) and relative risk applied to SCCA incidence. Of 30 416 SCCA estimated globally in 2020, two‐thirds occurred in women (19 792) and one‐third among men (10 624). Fifty‐three percent of male SCCA and 65% of female SCCA occurred in countries with a very high Human Development Index (HDI). Twenty‐one percent of the global male SCCA burden occurred in PLWHIV (n = 2203), largely concentrated in North America, Europe and Africa. While, only 3% of global female SCCA burden (n = 561) occurred in PLWHIV, mainly in Africa. The global age‐standardized incidence rate of HIV‐negative SCCA was higher in women (0.55 cases per 100 000) than men (0.28), whereas HIV‐positive SCCA was higher in men (0.07) than women (0.02). HIV prevalence reached >40% in 22 countries for male SCCA and in 10 countries for female SCCA, mostly in Africa. Understanding global SCCA burden by HIV status can inform SCCA prevention programs (through HPV vaccination, screening and HIV control) and help raise awareness to combat the disease.
TL;DR: Examination of global patterns of Hodgkin lymphoma in 2020 and predicts the future incidence and mortality burden in 2040 using IARC's GLOBOCAN estimates of the number of new cases and deaths in 185 countries shows incidence rates were consistently higher in males and mortality exhibited an inverse pattern compared to incidence.
Abstract: Our study examines global patterns of Hodgkin lymphoma (HL) in 2020 and predicts the future incidence and mortality burden in 2040 using IARC's GLOBOCAN estimates of the number of new cases and deaths of HL in 185 countries. A total of 83 000 new cases of HL and 23 000 deaths from HL were estimated in 2020. In general, incidence and mortality rates were consistently higher in males (50% more cases and deaths than females) across world regions and countries. Incidence rates varied markedly by world region, at least 10‐fold in both sexes, with the highest incidence rates observed in Southern Europe. Mortality exhibited an inverse pattern compared to incidence, with rates elevated in Western Asia and Northern Africa. The number of HL incident cases is predicted to rise to around 107 000 cases (a 30% increase) by 2040 due to demographic changes, assuming global rates in 2020 remains unchanged. The findings provide a baseline and impetus for developing strategies that aim to reduce the burden of HL in future decades.
TL;DR: In this article, the DNA methylation test (S5) was used to detect high-grade cervical intraepithelial neoplasia (CIN) and cancer, but also brings an improved specificity to avoid unnecessary clinical work and colposcopy referrals.
Abstract: The shift towards primary human papillomavirus (HPV)-based screening has necessitated the search for a secondary triage test that provides sufficient sensitivity to detect high-grade cervical intraepithelial neoplasia (CIN) and cancer, but also brings an improved specificity to avoid unnecessary clinical work and colposcopy referrals. We evaluated the performance of the previously described DNA-methylation test (S5) in detecting CIN3 and cancers from diverse geographic settings in high-, medium- and low-income countries, using the cut-off of 0.80 and exploratory cut-offs of 2.62 and 3.70. Assays were performed using exfoliated cervical specimens (n = 808) and formalin-fixed biopsies (n = 166) from women diagnosed with cytology-negative results (n = 220), CIN3 (n = 204) and cancer stages I (n = 245), II (n = 249), III (n = 28) and IV (n = 22). Methylation increased proportionally with disease severity (Cuzick test for trend, P < .0001). S5 accurately separated women with negative-histology from CIN3 or cancer (P < .0001). At the 0.80 cut-off, 543/544 cancers were correctly identified as S5 positive (99.81%). At cut-off 3.70, S5 showed a sensitivity of 95.77% with improved specificity. The S5 odds ratios of women negative for cervical disease vs CIN3+ were significantly higher than for HPV16/18 genotyping at all cut-offs (all P < .0001). At S5 cut-off 0.80, 96.15% of consistently high-risk human papillomavirus (hrHPV)-negative cancers (tested with multiple hrHPV-genotyping assay) were positive by S5. These cancers may have been missed in current primary hrHPV-screening programmes. The S5 test can accurately detect CIN3 and malignancy irrespective of geographic context and setting. The test can be used as a screening and triage tool. Adjustment of the S5 cut-off can be performed considering the relative importance given to sensitivity vs specificity.
TL;DR: It is suggested that the systemic responses to acute aerobic exercise inhibit colon cancer cell proliferation in vitro, and this may be driven by IL‐6‐induced regulation of DNA damage and repair.
Abstract: Epidemiological evidence shows that regular physical activity is associated with reduced risk of primary and recurrent colon cancer. However, the underlying mechanisms of action are poorly understood. We evaluated the effects of stimulating a human colon cancer cell line (LoVo) with human serum collected before and after an acute exercise bout vs nonexercise control serum on cancer cell proliferation. We also measured exercise‐induced changes in serum cytokines and intracellular protein expression to explore potential biological mechanisms. Blood samples were collected from 16 men with lifestyle risk factors for colon cancer (age ≥50 years; body mass index ≥25 kg/m2; physically inactive) before and immediately after an acute bout of moderate‐intensity aerobic interval exercise (6 × 5 minutes intervals at 60% heart rate reserve) and a nonexercise control condition. Stimulating LoVo cells with serum obtained immediately after exercise reduced cancer cell proliferation compared to control (−5.7%; P = .002). This was accompanied by a decrease in LoVo cell γ‐H2AX expression (−24.6%; P = .029), indicating a reduction in DNA damage. Acute exercise also increased serum IL‐6 (24.6%, P = .002). Furthermore, stimulating LoVo cells with recombinant IL‐6 reduced γ‐H2AX expression (β = −22.7%; P < .001) and cell proliferation (β = −5.3%; P < .001) in a linear dose‐dependent manner, mimicking the effect of exercise. These findings suggest that the systemic responses to acute aerobic exercise inhibit colon cancer cell proliferation in vitro, and this may be driven by IL‐6‐induced regulation of DNA damage and repair. This mechanism of action may partly underlie epidemiological associations linking regular physical activity with reduced colon cancer risk.
TL;DR: Novel insights are provided into mRNA vaccination efficacy in immunocompromised MM and CLL patients, and the findings highlight that specific CD8+ T cells against SARS‐CoV‐2 might be induced by vaccination but do not correlate positively with serological responses.
Abstract: Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients have increased morbidity and mortality rates of COVID‐19 due to immunosuppression associated with the disease and ongoing therapy. The same immune impairment accompanying CLL and MM also affects suboptimal vaccine response. The study assessed the effectiveness of the humoral and T cell‐mediated immunity following mRNA COVID‐19 vaccination (using either BNT162b2 or mRNA‐1273) in short‐term (2‐5 weeks after second dose) and long‐term follow‐up (12 weeks after vaccination). Between March and August 2021, blood samples were obtained from 62 CLL and 60 MM patients from eight different hematology departments in Poland. Total anti‐RBD antibodies were detected in 37% MM patients before vaccination, increased to 91% and 94% in short‐ and long‐term follow‐up, respectively. In CLL, serological responses were detectable in 21% of patients before vaccination and increased to 45% in the short‐term and 71% in long‐term observation. We detected a tendency to higher frequencies of specific CD8+ T cells against SARS‐CoV‐2 after vaccination compared to samples before vaccination in MM patients and no changes in frequencies of specific T cells in CLL patients. Our study provides novel insights into mRNA vaccination efficacy in immunocompromised MM and CLL patients, and our findings highlight that specific CD8+ T cells against SARS‐CoV‐2 might be induced by vaccination but do not correlate positively with serological responses.
TL;DR: The sex differences were consistent across time periods but varied significantly by age across the life span, and across the four cancer types, the male‐to‐female incidence rate ratios increased from young ages, approaching a peak at ages 60‐64, but sharply declined thereafter.
Abstract: A male predominance was observed in esophageal and gastric cancers, though present limited data has revealed variations by age. We aim to investigate the global age‐specific sex differences in esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Data on esophageal and gastric cancers incidence by diagnosis year, sex, histology, subsite and age group were extracted from 171 registries in 54 countries included in the last two volumes (X and XI, 2003‐2012) of Cancer Incidence in Five Continents, which contributing to over 80% of the global burdens of these cancers. Age‐standardized incidence rates (ASIRs) and male‐to‐female ASIRs ratios were estimated for esophageal and gastric cancers, by histological subtype and subsite, globally and by country. We consistently observed a male predominance in esophageal and gastric cancers across the world from 2003 to 2012, with male‐to‐female ASIRs ratios of 6.7:1 for EAC, 3.3:1 for ESCC, 4.0:1 for GCC and 2.1:1 for GNCC. The sex differences were consistent across time periods but varied significantly by age across the life span. Across the four cancer types, the male‐to‐female incidence rate ratios increased from young ages, approaching a peak at ages 60‐64, but sharply declined thereafter. Similar “low‐high‐low” trends of age‐specific sex ratio were observed in other digestive cancers including liver, pancreas, colon and rectum with peak ages ranging from 50 to 65. Age‐dependent risk factors warrant further investigation to aid our understanding of the underlying etiologies of esophageal and gastric cancers by histological subtype and subsite.
TL;DR: The prevalence of screen‐detected aggressive (ISUP ≥3) PCa in 45‐year‐old men is very low and DRE did not turn out effective for early detection of PCa.
Abstract: There is no generally accepted screening strategy for prostate cancer (PCa). From February 2014 to December 2019 a randomized trial (PROBASE) recruited 46 642 men at age 45 to determine the efficacy of risk‐adapted prostate‐specific antigen‐based (PSA) screening, starting at either 45 or 50 years. PSA tests are used to classify participants into a low (<1.5 ng/mL), intermediate (1.5‐2.99 ng/mL) or high (≥3 ng/mL) risk group. In cases of confirmed PSA values ≥3 ng/mL participants are recommended a prostate biopsy with multiparametric magnetic resonance imaging (mpMRI). Half of the participants (N = 23 341) were offered PSA screening immediately at age 45; the other half (N = 23 301) were offered digital rectal examination (DRE) with delayed PSA screening at age 50. Of 23 301 participants who accepted baseline PSA testing in the immediate screening arm, 89.2% fell into the low, 9.3% into intermediate, and 1.5% (N = 344) into the high risk group. Repeat PSA measurement confirmed high‐risk status for 186 men (0.8%), of whom 120 (64.5%) underwent a biopsy. A total of 48 PCas was detected (overall prevalence 0.2%), of which 15 had International Society of Uropathology (ISUP) grade 1, 29 had ISUP 2 and only 4 had ISUP ≥3 cancers. In the delayed screening arm, 23 194 participants were enrolled and 6537 underwent a DRE with 57 suspicious findings, two of which showed PCa (both ISUP 1; detection rate 0.03%). In conclusion, the prevalence of screen‐detected aggressive (ISUP ≥3) PCa in 45‐year‐old men is very low. DRE did not turn out effective for early detection of PCa.
TL;DR: The causal effects of alcohol consumption on upper aerodigestive tract cancers are supported, with ALDH2‐rs671 AG genotype further exacerbating the risks.
Abstract: Two genetic variants that alter alcohol metabolism, ALDH2‐rs671 and ADH1B‐rs1229984, can modify oesophageal cancer risk associated with alcohol consumption in East Asians, but their associations with other cancers remain uncertain. ALDH2‐rs671 G>A and ADH1B‐rs1229984 G>A were genotyped in 150 722 adults, enrolled from 10 areas in China during 2004 to 2008. After 11 years' follow‐up, 9339 individuals developed cancer. Cox regression was used to estimate hazard ratios (HRs) for site‐specific cancers associated with these genotypes, and their potential interactions with alcohol consumption. Overall, the A‐allele frequency was 0.21 for ALDH2‐rs671 and 0.69 for ADH1B‐rs1229984, with A‐alleles strongly associated with lower alcohol consumption. Among men, ALDH2‐rs671 AA genotype was associated with HR of 0.69 (95% confidence interval: 0.53‐0.90) for IARC alcohol‐related cancers (n = 1900), compared to GG genotype. For ADH1B‐rs1229984, the HRs of AG and AA vs GG genotype were 0.80 (0.69‐0.93) and 0.75 (0.64‐0.87) for IARC alcohol‐related cancers, 0.61 (0.39‐0.96) and 0.61 (0.39‐0.94) for head and neck cancer (n = 196) and 0.68 (0.53‐0.88) and 0.60 (0.46‐0.78) for oesophageal cancer (n = 546). There were no significant associations of these genotypes with risks of liver (n = 651), colorectal (n = 556), stomach (n = 725) or lung (n = 1135) cancers. Among male drinkers, the risks associated with higher alcohol consumption were greater among ALDH2‐rs671 AG than GG carriers for head and neck, oesophageal and lung cancers (Pinteraction < .02). Among women, only 2% drank alcohol regularly, with no comparable associations observed between genotype and cancer. These findings support the causal effects of alcohol consumption on upper aerodigestive tract cancers, with ALDH2‐rs671 AG genotype further exacerbating the risks.
TL;DR: In this article, the levels of multiple nuclear transport proteins secreted from cancer cells, and to determine their potential as diagnostic markers for cervical and oesophageal cancer, were investigated.
Abstract: Previous studies have identified increased expression of members of the nuclear transport protein family in cancer cells. Recently, certain nuclear transport proteins have been reported to be secreted by cells and found in the serum. The aims of our study were to investigate the levels of multiple nuclear transport proteins secreted from cancer cells, and to determine their potential as diagnostic markers for cervical and oesophageal cancer. Mass spectrometry identified 10 nuclear transport proteins in the secretome and exosomes of cultured cancer cells, and Western blot analysis confirmed increased secreted levels in cancer cells compared to normal. To investigate their presence in patient serum, enzyme-linked immunosorbent assays were performed and revealed significantly increased levels of KPNβ1, CRM1, CAS, IPO5 and TNPO1 in cervical and oesophageal cancer patient serum compared to non-cancer controls. Significantly elevated KPNα2 and RAN levels were also identified in oesophageal cancer serum samples. Logistics regression analyses revealed IPO5 and TNPO1 to be the best performing individual candidate biomarkers in discriminating between cancer cases and controls. The combination of KPNβ1, CRM1, KPNα2, CAS, RAN, IPO5 and TNPO1 as a panel of biomarkers had the highest diagnostic capacity with an area under the curve of 0.944 and 0.963, for cervical cancer and oesophageal cancer, and sensitivity of 92.5% at 86.8% specificity and 95.3% sensitivity at 87.5% specificity, respectively. These results suggest that nuclear transport proteins have potential as diagnostic biomarkers for cervical and oesophageal cancers, with a combination of protein family members being the best predictor.
TL;DR: In this paper, the authors evaluated the diagnostic performance of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) and cancer of unknown primary (CUP) in blood samples.
Abstract: A biomarker that is useful for the detection of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) and cancer of unknown primary (CUP) is indispensable. We evaluated the diagnostic performance of HPV DNA and mRNA in oral gargle samples and circulating tumor HPV16 DNA (ctHPV16DNA) in blood samples. Oral HPV DNA and mRNA were analyzed using commercially available HPV assays of the GENOSEARCH HPV31 and Aptima, respectively. ctHPV16DNA was analyzed using in-house droplet digital PCR. Seventy-four patients with OPC and eight patients with CUP were included. The sensitivity and specificity of oral HPV DNA, oral HPV mRNA, and ctHPV16DNA were 82% (95% confidence interval [CI], 66-92) and 100% (95% CI, 88-100), 85% (95% CI, 69-94) and 94% (95% CI, 73-100), and 93% (95% CI, 81-99) and 97% (95% CI, 84-100), respectively, for HPV16-related OPC, while those were 20% (95% CI, 1-72) and 100% (95% CI, 3-100), 0% (95% CI, 0-52) and 100% (95% CI, 3-100), and 100% (95% CI, 54-100) and 100% (95% CI, 16-100), respectively, for HPV16-related CUP. The sensitivity of ctHPV16DNA for HPV16-related OPC was higher than that of oral biomarkers, though the difference was not statistically significant. ctHPV16DNA remarkably correlated with the anatomic extent of disease, total metabolic tumor volume, and HPV16 copy number per tumor genome in patients with HPV16-related OPC/CUP, whereas oral biomarkers did not. In conclusion, ctHPV16DNA is a potentially promising biomarker for HPV16-related OPC, while further studies are required for HPV16-related CUP. This article is protected by copyright. All rights reserved.
TL;DR: Tumor stage at initial presentation, emergency level of primary tumor resection, delays between the first multidisciplinary meeting and the first anticancer treatment did not differ over time, and the SARS‐Cov2 pandemic has been associated with less newly diagnosed CRC patients and worse 1‐year OS rates.
Abstract: The SARS‐Cov2 may have impaired care trajectories, patient overall survival (OS), tumor stage at initial presentation for new colorectal cancer (CRC) cases. This study aimed at assessing those indicators before and after the beginning of the pandemic in France. In this retrospective cohort study, we collected prospectively the clinical data of the 11.4 million of patients referred to the Greater Paris University Hospitals (AP‐HP). We identified new CRC cases between 1 January 2018 and 31 December 2020, and compared indicators for 2018‐2019 to 2020. pTNM tumor stage was extracted from postoperative pathology reports for localized colon cancer, and metastatic status was extracted from CT‐scan baseline text reports. Between 2018 and 2020, 3602 and 1083 new colon and rectal cancers were referred to the AP‐HP, respectively. The 1‐year OS rates reached 94%, 93% and 76% for new CRC patients undergoing a resection of the primary tumor, in 2018‐2019, in 2020 without any Sars‐Cov2 infection and in 2020 with a Sars‐Cov2 infection, respectively (HR 3.78, 95% CI 2.1‐7.1). For patients undergoing other kind of anticancer treatment, the percentages are 64%, 66% and 27% (HR 2.1, 95% CI 1.4‐3.3). Tumor stage at initial presentation, emergency level of primary tumor resection, delays between the first multidisciplinary meeting and the first anticancer treatment did not differ over time. The SARS‐Cov2 pandemic has been associated with less newly diagnosed CRC patients and worse 1‐year OS rates attributable to the infection itself rather than to its impact on hospital care delivery or tumor stage at initial presentation.
TL;DR: In this paper, a Cox proportional hazards model was used for overall survival by considering identified phenotypes (latent classes) and other confounding variables, and a pan-cancer nomogram model to predict survival (STARS: site, tumor, age, race, sex) was created, validated and provided 13% better prognostication than AJCC: 1-month concordance index of 0.67 (95% confidence interval [CI]: 0.60-0.61).
Abstract: Although cancer is highly heterogeneous, all metastatic cancer is considered American Joint Committee on Cancer (AJCC) Stage IV disease. The purpose of this project was to redefine staging of metastatic cancer. Internal validation of nationally representative patient data from the National Cancer Database (n = 461 357; 2010-2013), and external validation using the Surveillance, Epidemiology and End Results database (n = 106 595; 2014-2015) were assessed using the concordance index for evaluation of survival prediction. A Cox proportional hazards model was used for overall survival by considering identified phenotypes (latent classes) and other confounding variables. Latent class analysis was performed for phenotype identification, where Bayesian information criterion (BIC) and sample-size-adjusted BIC were used to select the optimal number of distinct clusters. Kappa coefficients assessed external cluster validation. Latent class analysis identified five metastatic phenotypes with differences in overall survival (P < .0001): (Stage IVA) nearly exclusive bone-only metastases (n = 59 049, 12.8%; median survival 12.7 months; common in lung, breast and prostate cancers); (IVB) predominant lung metastases (n = 62 491, 13.5%; 11.4 months; common in breast, stomach, kidney, ovary, uterus, thyroid, cervix and soft tissue cancers); (IVC) predominant liver/lung metastases (n = 130 014, 28.2%; 7.0 months; common in colorectum, pancreatic, lung, esophagus and stomach cancers); (IVD) bone/liver/lung metastases predominant over brain (n = 61 004, 13.2%; 5.9 months; common in lung and breast cancers); and (IVE) brain/lung metastases predominant over bone/liver (n = 148 799, 32.3%; 5.7 months; lung cancer and melanoma). Long-term survivors were identified, particularly in Stages IVA-B. A pan-cancer nomogram model to predict survival (STARS: site, tumor, age, race, sex) was created, validated and provides 13% better prognostication than AJCC: 1-month concordance index of 0.67 (95% confidence interval [CI]: 0.66-0.67) vs 0.61 (95% CI: 0.60-0.61). STARS is simple, uses easily accessible variables, better prognosticates survival outcomes and provides a platform to develop novel metastasis-directed clinical trials.
TL;DR: The results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups, with null associations in MR analysis.
Abstract: Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone‐binding globulin (SHBG) with aggressive, overall and early‐onset prostate cancer. In blood‐based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse‐variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08‐1.40). In blood‐based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02‐1.28; Phet = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08‐1.34; blood‐based: 1.03, 1.01‐1.05) and early‐onset prostate cancer (MR: 1.37, 1.09‐1.73; blood‐based: 1.08, 0.98‐1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood‐based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.
TL;DR: There was limited-suggestive evidence that predefined dietary patterns may reduce the risk of all-cause and other causes of death; that isoflavone intake reduces therisk ofall-cause mortality; and that serum 25(OH)D is inversely associated with all- Cause and breast cancer-specific mortality.
Abstract: Little is known about how diet might influence breast cancer prognosis. The current systematic reviews and meta‐analyses summarise the evidence on postdiagnosis dietary factors and breast cancer outcomes from randomised controlled trials and longitudinal observational studies. PubMed and Embase were searched through 31st October 2021. Random‐effects linear dose‐response meta‐analysis was conducted when at least three studies with sufficient information were available. The quality of the evidence was evaluated by an independent Expert Panel. We identified 108 publications. No meta‐analysis was conducted for dietary patterns, vegetables, wholegrains, fish, meat, and supplements due to few studies, often with insufficient data. Meta‐analysis was only possible for all‐cause mortality with dairy, isoflavone, carbohydrate, dietary fibre, alcohol intake and serum 25‐hydroxyvitamin D (25(OH)D), and for breast cancer‐specific mortality with fruit, dairy, carbohydrate, protein, dietary fat, fibre, alcohol intake and serum 25(OH)D. The results, with few exceptions, were generally null. There was limited‐suggestive evidence that predefined dietary patterns may reduce the risk of all‐cause and other causes of death; that isoflavone intake reduces the risk of all‐cause mortality (relative risk (RR) per 2 mg/day: 0.96, 95% confidence interval (CI): 0.92‐1.02), breast cancer‐specific mortality (RR for high vs low: 0.83, 95% CI: 0.64‐1.07), and recurrence (RR for high vs low: 0.75, 95% CI: 0.61‐0.92); that dietary fibre intake decreases all‐cause mortality (RR per 10 g/day: 0.87, 95% CI: 0.80‐0.94); and that serum 25(OH)D is inversely associated with all‐cause and breast cancer‐specific mortality (RR per 10 nmol/L: 0.93, 95% CI: 0.89‐0.97 and 0.94, 95% CI: 0.90‐0.99, respectively). The remaining associations were graded as limited‐no conclusion.