BACKGROUND:Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. METHODS:Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) <0.2 was used to identify associations with strong statistical evidence. RESULTS:Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend<0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend<0.001 and <0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend<0.001 and <0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. CONCLUSION:This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.

BACKGROUND:Despite improvements in primary breast cancer treatment, 10-year cumulative locoregional recurrence (LRR) incidence is around 8%. This study aimed to examine the management of patients diagnosed with LRR. METHODS:Patients previously treated for breast cancer and diagnosed with LRR were prospectively identified at breast MDT meetings and clinics. Data collection included tumour pathology, imaging results, surgical treatment, and adjunct therapy for the original and recurrent cancer. RESULTS:Data were analysed for 742 patients recruited from 50 UK hospitals (2022-2023). Median ages at original cancer (OC) and LRR diagnosis were 53 and 67 years old respectively; median disease-free interval (DFI) 8.9 years. For the OC and LRR, ER + PR + HER2-receptor profile was most prevalent. Breast conserving surgery (BCS) was predominantly performed for the OC (75.3%; 559/742). Concomitant distant metastases (DM) rate was 9.3% (69/742) with higher incidence seen in node positive LRR, HER2+ LRR, and shorter DFI (<5 years). Of 622 patients receiving LRR resection, commonest procedures were mastectomy (62.9%; 391/622), wide excision of chest wall/skin flap LRR (20.6%; 128/622), and repeat BCS (10.9%; 68/622). For patients receiving axillary surgery, node positivity rate was 25.3% (140/554) for OC and 21.3% (86/403) for LRR. Radiotherapy (67.8% OC vs. 18.8% LRR) and chemotherapy (33.1% OC vs. 23.9% LRR) utilisation rates were lower for LRR. Endocrine therapy utilisation rate was higher for LRR (63.5% OC and 70.5% LRR). CONCLUSION:Routine radiological staging investigation is advocated for invasive LRR. Majority of LRR were resectable, with nodal positivity rate comparable to the original cancer.

Women with BRCA1/2 pathogenic variants (PVs) have a high likelihood of developing young onset breast cancer (BC) compared to noncarriers. In women enrolled in the POSH prospective cohort study of young women diagnosed with BC under age 40 or under age 50 if known BRCA1/2 positive, no difference in overall survival was observed in BRCA1/2 carriers vs noncarriers. Treatment options for BC include PARP inhibitors (PARPi) for BRCA1/2 driven tumors and CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy for ER-positive, HER2-negative tumors. In BC from BRCA1/2 carriers unselected for age, up to 10% BRCA1 and 46% BRCA2 carriers do not have loss of heterozygosity (LOH) at the germline variant locus, suggesting non-BRCA1/2 tumorigenesis. It is not known what the tumor molecular landscape, including rates of LOH and homologous recombination deficiency (HRD), is in young BRCA1/2 PV carriers with BC, and whether the tumor molecular features impact disease outcomes or predict therapy response. To elucidate the molecular landscape of breast tumors in young women with BRCA1/2 PVs, we evaluated treatment naïve primary breast tumors from 136 (86 [63.2%] BRCA1; 50 [36.8%] BRCA2) PV carriers in the POSH study. 71 (52.2%) of the tumors were ER-positive. We performed whole exome sequencing and called single nucleotide variants, indels, copy number variants, and BRCA1/2 allele specific LOH in the tumors, calculated HRD scores and tumor mutational burden (TMB), and evaluated single base substitution (SBS) signatures. We found high rates of LOH by gene: BRCA1 (93%) and BRCA2 (96%), and by ER-status: ER-negative (94.4%) and ER-positive (93.8%). Mean HRD scores were significantly higher in tumors with LOH compared to nonLOH tumors in both BRCA1 (57.4 vs 22.6, p<0.0001) and BRCA2 (43.7 vs 23.5, p=0.005) carriers as well as ER-negative (57.6 vs 22.8, p<0.0001) and ER-positive tumors (46.4 vs 22.8, p<0.001). LOH tumors had higher proportional contribution of HRD-associated SBS3 than nonLOH tumors (0.36 vs 0.22, p=0.048). BRCA1 LOH tumors had higher median TMB than BRCA2 LOH tumors (4.8 vs 2.5, p=0.034). Overall survival in women with nonLOH tumors was 100% throughout the follow-up period but was not significantly different from that of women with LOH tumors. Overall survival did not differ by tumor HRD status: analyses were limited by small numbers in the non-LOH and low HRD groups. We found statistically significant enrichment of AURKA (OR:4.2, 95%CI:1.3-16.6, p=0.015) and MYC (OR:2.4, 95%CI:1.0-5.7, p=0.043) amplification which are associated with resistance to CDK4/6i in ER-positive, HER2-negative tumors from POSH cohort PV carriers compared to noncarriers from the TCGA. Given the high levels of LOH and presence of CDK4/6i resistance associated alterations, our data suggest that PARPi may be preferable over CDK4/6i in young BRCA1/2 carriers with ER-positive, HER2-negative BC when both therapies are being considered in the adjuvant setting. Mwangala P. Akamandisa, Mingyi Xia, Wilson Cheah, Bradley Wubbenhorst, Kurt D'Andrea, Mengyao Fan, Jake Shilan, William J. Tapper, Ellen Copson, Ramsey I. Cutress, Diana M. Eccles, Susan M. Domchek, Katherine L. Nathanson. Tumor molecular landscape and therapy implications in young BRCA1/2 carriers with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6596.

Background The 2018 World Cancer Research Fund/American Institute for Cancer Research Third Expert Report, including studies up to 2015, determined limited–no conclusion evidence on dietary patterns and colorectal cancer (CRC) risk due to insufficient data and varying pattern definitions. Objectives This updated review synthesized literature on dietary patterns and CRC risk/mortality. Methods PubMed and Embase were searched through 31 March, 2023, for randomized controlled trials (RCTs) and prospective cohort studies on adulthood dietary patterns. Patterns were categorized by derivation method: a priori, a posteriori, or hybrid, and were then descriptively reviewed in relation to the primary outcomes: CRC risk or mortality. The Global Cancer Update Programme Expert Committee and Expert Panel independently graded the evidence on the likelihood of causality using predefined criteria. Results Thirty-two dietary scores from 53 observational studies and 3 RCTs were reviewed. Limited–suggestive evidence was concluded for higher alignment with a priori–derived patterns: Mediterranean, healthful plant-based index, Healthy Eating Index (HEI)/alternate HEI, and Dietary Approaches to Stop Hypertension (DASH), in relation to lower CRC risk. Common features across these diets included high plant-based food intake and limited red/processed meat. Hybrid-derived patterns: the empirical dietary index for hyperinsulinemia (EDIH) and the empirical dietary inflammatory pattern (EDIP), showed strong–probable evidence for increased CRC risk. Evidence for a priori–derived low-fat dietary interventions and a posteriori–derived patterns was graded as limited–no conclusion. By cancer subsite, higher alignment with Mediterranean diet showed limited–suggestive evidence for lower rectal cancer risk, and that with HEI/alternate HEI and DASH showed limited–suggestive evidence for lower colon and rectal cancer risks. EDIH and EDIP showed strong–probable evidence for increased colon cancer risks. All exposure–mortality pairs and other pattern–outcome associations were graded as limited–no conclusion. Conclusions This review highlights the role of dietary patterns in CRC risk/mortality, providing insights for future research and public health strategies.This review was registered at PROSPERO as CRD42022324327 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324327).

While adult anthropometric measures are well-studied in relation to colorectal cancer (CRC) risk, the impact of early-life anthropometry remains unclear. We conducted a systematic literature review and meta-analysis examining early-life anthropometry, including birth size, height and adiposity and adult CRC risk. We searched Medline, Embase, Web of Science and CENTRAL. Early-life stages were categorised as at birth, infancy (0 to <2 years), childhood (2 to 9 years), adolescence (10 to 19 years) and young adulthood (18 to 25 years). Random-effects meta-analyses were conducted when ≥3 prospective observational studies provided sufficient information; otherwise, results were descriptively synthesised. We included 37 publications, and evidence was graded by the Global Cancer Update Programme Expert Panel. Higher birthweight (relative risk [RR] per 1000 g: 1.09, 95% confidence interval [CI] 1.01-1.16; 8 studies, 8134 cases) and young adult body mass index (BMI, RR per 5 kg/m2: 1.12, 95% CI 1.07-1.17; 16 studies, 20,365 cases) were associated with higher CRC risk. Associations for young adult BMI were most pronounced for colon cancer (RR per 5 kg/m2: 1.15, 95% CI: 1.06-1.24). Descriptive synthesis showed that childhood and adolescent BMI were also associated with higher colon and/or CRC risk. Evidence for all the above associations was graded by the Expert Panel as "strong-probable." Additionally, there was "limited-suggestive" evidence linking higher birthweight to higher colon cancer risk, taller childhood height to higher CRC risk, early-life adiposity-measured by BMI pictograms-to higher colon and CRC risk and higher young adult BMI to rectal cancer risk. Other exposure-outcome associations were graded as "limited-no conclusion." Altogether, these results imply that larger body size during early life is associated with higher adult CRC risk.

BACKGROUND:Breast cancer is the most frequently diagnosed cancer in women. Survival is generally considered favourable, yet some patients remain at risk of early death. We aimed to assess whether comprehensive whole-genome sequencing (WGS) linked to mortality data could add prognostic value to existing clinical measures and identify patients who might respond to targeted therapeutics. METHODS:In this integrative, retrospective analysis, we analysed 2445 breast cancer tumours (any stage and molecular subtype) collected from 2403 patients recruited through 13 National Health Service Genomic Medicine Centres or hospitals in England affiliated to the 100 000 Genomes Project (100kGP) between 2012 and 2018. We linked 2208 (90%) cases with clinical data; mortality data were obtained for 1188 patients. Following high-depth WGS of tumour and matched normal DNA, we performed comprehensive WGS profiling seeking driver mutations, mutational signatures, and compound algorithmic scores for homologous recombination repair deficiency (HRD), mismatch repair deficiency, and tumour mutational burden. Data from 1803 additional patients with breast cancer from three independent cohorts were used to validate various findings. To evaluate the prognostic value of WGS features, we performed univariable and multivariable Cox regression on data from patients with stage I-III, ER-positive, HER2-negative breast cancer with a cancer-specific mortality endpoint (around 5-year follow-up). FINDINGS:Among 2445 tumours in the 100kGP breast cancer cohort, we observed genomic characteristics with immediate personalised medicine potential in 656 (26·8%), including features reporting HRD (298 [12·2%] total cases and 76 [6·3%] ER-positive, HER2-negative cases), highly individualised driver events, mutations underpinning resistance to endocrine therapy, and mutational signatures indicating therapeutic vulnerabilities. 373 (15·2%) cases had WGS features with potential for translational research, including compromised base excision repair and non-homologous end-joining dependency. Structural variation burden (hazard ratio 3·9 [95 CI% 2·4-6·2]; p<0·0001), high levels of APOBEC signatures (2·5 [1·6-4·1]; p<0·0001), and TP53 drivers (3·9 [2·4-6·2]; p<0·0001) were independently prognostic of customary clinical measures (age at diagnosis, stage, and grade) in patients with ER-positive, HER2-negative breast cancer. We developed a prognosticator for ER-positive, HER2-negative breast cancer capable of identifying patients who require either increased intervention or therapy de-escalation, validating the framework in the independent Swedish Cancerome Analysis Network-Breast (SCAN-B) dataset. INTERPRETATION:We show that breast cancer genomes are rich in predictive and prognostic value. We propose a two-step model for effective clinical application. First, the identification of candidates for targeted therapies or clinical trials using highly individualised genomic markers. Second, for patients without such features, the implementation of enhanced prognostication using genomic features alongside existing clinical decision-making factors. FUNDING:National Institute of Health Research, Breast Cancer Research Foundation, Dr Josef Steiner Cancer Research Award 2019, Basser Gray Prime Award 2020, Cancer Research UK, Sir Jeffrey Cheah Early Career Fellowship, the Mats Paulsson Foundation, the Fru Berta Kamprads Foundation, and the Swedish Research Council.

BACKGROUND:The impact of physical activity, sedentary behaviour, diet, adiposity, and body composition on health-related quality of life (HRQoL) and cancer-related fatigue among colorectal cancer survivors remains uncertain. METHODS:PubMed, Embase, and CENTRAL were systematically searched until April 2023 for relevant randomised controlled trials (RCTs) and cohort studies. Random-effects meta-analyses or descriptive syntheses were conducted depending on the number of studies. The evidence was interpreted and graded by an independent World Cancer Research Fund Expert Committee and Expert Panel. RESULTS:We included 31 RCTs (18 exercise, 14 diet) and 30 cohort studies (8 physical activity, 3 sedentary behaviour, 13 diet, 9 adiposity and body composition). Meta-analyses were possible for exercise RCTs that showed non-significant effects but indicative of improved HRQoL (overall four trials for global HRQoL, physical and emotional well-being) and fatigue (five trials). These studies were rated at a high risk of bias (RoB), and evidence was graded as 'very low certainty of an effect'. Descriptive synthesis of interventions to improve diet quality suggested small improvements in global HRQoL and physical well-being, but with a high RoB rating leading to a 'low certainty' grading. Evidence from RCTs on probiotics and supplements and evidence from observational studies on sedentary behaviour, and various dietary and body composition factors was generally inconsistent and too scarce to draw conclusions. CONCLUSIONS:Exercise and diet quality interventions might improve HRQoL and fatigue outcomes in colorectal cancer survivors. The evidence overall was limited and should be strengthened by larger, well-designed RCTs across the cancer continuum.

This Review presents a comprehensive analysis of the amounts and distribution of public and philanthropic global cancer research funding between 2016 and 2023, including patterns of international collaboration and downstream research output, with an emphasis on the Commonwealth. We show that annual investment decreased globally each year, apart from a rise in 2021. Network analysis revealed that grant and publication collaborations between the Commonwealth, the USA, and the EU are facilitated by linkages through a core group of Commonwealth countries, including the UK, Australia, and Canada. There are inequities in research investment and low funding for treatment modalities for many cancers. These inequities also manifest in the central positioning of high-income Commonwealth countries in research collaborations, but also point to opportunities for high-income Commonwealth countries to facilitate linkages with low-income countries and support active cancer research in the USA and the EU. There is an urgent need to review research investment priorities, both within the Commonwealth and globally, to align with population needs and promote collaborative strategies that can build research skills and infrastructure in low-income settings to impact global cancer control. Finite resources should be invested wisely to achieve maximum improvements in mortality and alleviate the cancer burden.

Obesity is associated with worse breast cancer outcomes and decreased therapeutic efficacy. However, the mechanisms driving obesity-associated therapy resistance remain unclear; in part due to a lack of suitable models that recapitulate the obese tumour microenvironment. To address this, we developed a 3D in vitro model of obesity-associated breast cancer, to investigate biological mechanisms and to use as a drug testing tool. A penta-culture system was developed by co-culturing adipocyte spheroids with breast tumour cells, myoepithelial cells, macrophages, and fibroblasts in a collagen matrix. Tumour cells and macrophages infiltrated adipocyte spheroids, replicating the inflamed-adipose border typical of obese patients. This model was then assessed as a drug testing platform. Obese cultures exhibited increased sensitivity to metformin and, conversely, resistance to paclitaxel, compared to non-obese cultures. This 3D organotypic model effectively recapitulates key features of the obese adipose tumour microenvironment, providing a useful tool to interrogate mechanisms underpinning obesity-related therapy resistance.

Background: The 2018 World Cancer Research Fund/American Institute for Cancer Research Third Expert Report, including studies up to 2015, determined limited-no conclusion evidence on dietary patterns and colorectal cancer (CRC) risk due to insufficient data and varying pattern definitions. Objectives: This updated review synthesized literature on dietary patterns and CRC risk/mortality. Methods: PubMed and Embase were searched through 31 March, 2023, for randomized controlled trials (RCTs) and prospective cohort studies on adulthood dietary patterns. Patterns were categorized by derivation method: a priori, a posteriori, or hybrid, and were then descriptively reviewed in relation to the primary outcomes: CRC risk or mortality. The Global Cancer Update Programme Expert Committee and Expert Panel independently graded the evidence on the likelihood of causality using predefined criteria. Results: Thirty-two dietary scores from 53 observational studies and 3 RCTs were reviewed. Limited-suggestive evidence was concluded for higher alignment with a priori-derived patterns: Mediterranean, healthful plant-based index, Healthy Eating Index (HEI)/alternate HEI, and Dietary Approaches to Stop Hypertension (DASH), in relation to lower CRC risk. Common features across these diets included high plant-based food intake and limited red/ processed meat. Hybrid-derived patterns: the empirical dietary index for hyperinsulinemia (EDIH) and the empirical dietary inflammatory pattern (EDIP), showed strong-probable evidence for increased CRC risk. Evidence for a priori-derived low-fat dietary interventions and a posteriori-derived patterns was graded as limited-no conclusion. By cancer subsite, higher alignment with Mediterranean diet showed limited-suggestive evidence for lower rectal cancer risk, and that with HEI/alternate HEI and DASH showed limited-suggestive evidence for lower colon and rectal cancer risks. EDIH and EDIP showed strong-probable evidence for increased colon cancer risks. All exposure-mortality pairs and other pattern-outcome associations were graded as limited-no conclusion. Conclusions: This review highlights the role of dietary patterns in CRC risk/mortality, providing insights for future research and public health strategies. This review was registered at PROSPERO as CRD42022324327 (https://www.crd.york.ac.uk/prospero/display_record.php?ID1/4CRD42022324327).

Whole Genome Sequencing (WGS) provides comprehensive genomic profiling of brain tumours. In Wessex, the integration of WGS into clinical workflow has been adopted rapidly to enable this emerging clinical tool. This requires multi-speciality working and the support of a dedicated Genomics Medicine team. This project reviews the current WGS pathway infrastructure within a large tertiary UK neuro-oncology unit. Patients with primary brain tumours eligible for WGS as per NHS/GLH criteria were identified from theatre lists between January-December 2024. Electronic patient records, histopathological reports and WGS reports were analysed. Rates of adequate sample collection and completed WGS reports were recorded. Uncompleted WGS reports were analysed for root cause. Pre-operative clinical assessment of patients undergoing surgical intervention for a primary brain tumour in- cludes discussion of WGS testing. 104 patients were identified as eligible for WGS. Of these, 70 (67.3%) had ade- quate frozen tissue taken at time of surgery to facilitate WGS. The Genomics Medicine team consent patients to WGS and track samples from the point of collection to ensure all samples proceed. From the samples collected, all have progressed to one of three categories: WGS report, low DNA content, clinical reason to abandon test- ing. The weekly GTAB meeting led by the Genomics Medicine team and clinical scientists works closely with clinicians to interpret results and identify potential therapeutic targets/clinical trials. A review to investigate barriers to adequate sample collection/uncompleted WGS is ongoing. BNOS and Darzi reports separately recommend the routine use of WGS for all patients with primary brain tumours. This audit demonstrates the rapid adoption of the this tool in clinical practice with a robust multi- disciplinary clinical pathway. The Genomics Medicine team facilitate sample processing to a conclusion in all instances and are imperative to WGS interpretation.

BACKGROUND:Clinical research is key to improving the outcomes of patients with metastatic breast cancer (MBC). However, participation is low, with little data on patients' attitudes and experiences of clinical research. This study aimed to explore the experience and attitude of patients in accessing and participating in clinical research in the UK. METHODS:An online survey, available between May and November 2021, was open to people living with MBC in the UK; this was complemented with by qualitative interviews. FINDINGS:768 responses were received (766 female, 2 male); median age was 51-60 years with 235 (31 %) having de novo disease. 660 (86 %) respondents were confident in their understanding of clinical research. Discussion of participation in research with an oncologist was reported by 173 (23 %) respondents. Accessing new treatments was the most common reason for study participants wanting to take part in research, 737 (96 %). Of the 107 (14 %) respondents who had taken part in clinical trials, 77 (72 %) reported a positive experience. 276 (36 %) would consider travelling to participate in research and 430 (56 %) would be more likely to travel if expenses were met. Themes emerging from the qualitative interviews include 'lack of information', 'barriers to participation' and 'participants research priorities'. INTERPRETATION:This is the largest UK prospective study in regards to the views of MBC patients towards research. It demonstrates keenness to be involved in research, but participants face barriers as well as a lack of opportunity for participation. Key messages include importance of clinical staff in providing research information, need to develop patient accessible information, and to support travel costs. Improvements within the UK health care system are necessary to enable MBC patients to have equitable access to clinical research.

The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post-diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random-effects dose-response meta-analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all-cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease-free events). Meta-analyses, including 3-10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega-3 polyunsaturated fatty acids, supplemental calcium, circulating 25-hydroxyvitamin D (25[OH]D) and all-cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer-specific mortality; and for circulating 25(OH)D and recurrence/disease-free survival. The overall evidence was graded as 'limited'. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), whole grains, total, caffeinated, or decaffeinated coffee and all-cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all-cause mortality provided 'limited-suggestive' evidence. All other exposure-outcome associations provided 'limited-no conclusion' evidence. Additional, well-conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors.

Background An increasing number of studies in recent years investigate various dietary and lifestyle patterns and associated breast cancer (BC) risk. Objectives This study aimed to comprehensively synthesize and grade the evidence on dietary and lifestyle patterns and BC risk. Methods Databases were systematically searched up to 31 March, 2022, for evidence from randomised controlled trials and prospective cohort studies on adherence to a dietary pattern alone or in combination with lifestyle behaviors and incidence of or mortality from primary BC in adult females. Findings in all, premenopausal, and postmenopausal females were descriptively synthesized instead of meta-analyzed due to patterns heterogeneity. An independent Global Cancer Update Programme Expert Panel graded the strength of the evidence. Results A total of 84 publications were included. Results for patterns reflecting both a healthy diet and lifestyle were more consistent than for patterns that included diet only. There was strong-probable evidence that a priori World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) and American Cancer Society (ACS) dietary and lifestyle scores may reduce BC risk in all and postmenopausal females, whereas in premenopausal females, less evidence was found contributing to limited-suggestive grade. There was also a limited-suggestive evidence that adherence to the Healthy Lifestyle Index and other diet and lifestyle scores may reduce BC risk in postmenopausal females; a posteriori Western/Meat/Alcohol dietary patterns may increase BC risk in postmenopausal females; and Prudent/Vegetarian/Mediterranean dietary patterns may reduce BC risk in all females. For the remaining patterns, evidence was graded as limited-no conclusions. Conclusions Advice to adopt combined aspects of a healthy diet and lifestyle according to WCRF/AICR and ACS scores, encouraging a healthy weight, physical activity, alcohol and smoking avoidance, and a healthy diet rich in fruits, vegetables, (whole)grains and cereals and discouraging red and processed meat, can be proposed to females to lower BC risk.This review was registered at PROSPERO as ID CRD42021270129 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021270129) on 28 August, 2021, and further updated on 4 May, 2022, in order to extend the search period.