Tibolone, a synthetic steroid with estrogenic, progestogenic, and androgenic activity, is widely prescribed for menopausal symptoms, but its association with hepatocellular carcinoma (HCC) remains unclear. Using data from 117,271 women aged ≥ 45 years in the Korean National Health Insurance Service-Health Screening Cohort, we evaluated tibolone use between 2003 and 2007 and identified incident HCC from 2009 through 2019, implementing a 1-year lag period. Participants were propensity score-matched (1:10) by demographic, lifestyle, and metabolic factors. During a median 11-year follow-up, women with ≥ 180 cumulative days of tibolone use showed a higher HCC risk compared with non-users (hazard ratio [HR], 1.88; 95% CI, 1.07-3.29), which persisted after adjustment for key covariates (adjusted hazard ratio [aHR], 1.74; 95% CI, 0.99-3.06). A dose-response trend was observed (P for trend = 0.043). These findings suggest a possible link between sustained tibolone use and HCC risk, warranting confirmation in larger populations and longer follow-up, ideally through well-designed prospective studies.
Whether combining pretreatment plasma Epstein-Barr virus DNA (EBV-DNA) with 18F-FDG PET/CT-derived total lesion glycolysis (TLG) improves prognostic stratification in nonmetastatic nasopharyngeal carcinoma (NPC) is unclear, particularly in nonendemic populations. We retrospectively analyzed 86 eligible nonmetastatic NPC patients treated with definitive radiotherapy (2010-2024) at a single nonendemic-region institution. EBV-DNA (prespecified cutoff 3500 copies/mL) and TLG (cutoff 200, ROC-derived within this cohort) were dichotomized. Both were available in 59/86 patients (68.6%), who differed from the rest in nodal and overall stage and in RT technique. Baseline PET/CT was in-house in 57 of 86 patients, and a robustness analysis in that subgroup is reported. Given limited events (13 PFS, 9 OS), Cox analyses are exploratory and were supplemented with penalized regression and bootstrap validation. At a median follow-up of 75.5 months, 5-year PFS and OS for the whole cohort (n = 86) were 81.1% and 85.9%. The EBV-DNAhigh/TLGhigh subgroup remained associated with inferior PFS after adjustment in an exploratory model (adjusted HR = 3.97, 95% CI: 1.32-11.93) and, in a single-variable model, with inferior OS (HR = 4.13, 95% CI: 1.10-15.52). Discrimination was comparable to the individual-biomarker model for PFS and lower for OS. Five-year PFS fell monotonically across the four risk groups in the complete-case cohort (n = 59; 89.7%-58.3%). OS differed across groups (log-rank p = 0.044) but was not strictly monotonic, with wide, overlapping confidence intervals. This two-biomarker model is hypothesis-generating and needs prospective, multicenter validation before any consideration of risk-adapted treatment.
The optimal follow-up strategy for patients with locally advanced gastric cancer (LAGC) receiving neoadjuvant therapy (NAT) remains unknown. Traditional follow-up strategies based on relatively fixed intervals fail to fully account for dynamic changes in recurrence risk. This study aimed to develop a personalized postoperative follow-up strategy using dynamic programming (DP) to optimize follow-up arrangements based on individual patient characteristics and dynamic recurrence risks. This study included 3397 patients with LAGC who underwent surgery after NAT at 21 medical centers between 2018 and 2023. By integrating multiple prognostic indicators using a random survival forest model, we estimated individual time-adjusted cumulative hazards. A conditional inference tree was then used to stratify patients into low-, medium-, and high-risk groups. The DP algorithm was employed to determine the optimal follow-up arrangements for recurrence detection. A Markov decision-analytic model was used to identify the most cost-effective follow-up strategy. Compared with the guideline strategies, the DP-based strategy significantly reduced the average delayed detection time, particularly in the high-risk group. Furthermore, the cost-effectiveness analysis showed that the DP-based strategy achieved the best incremental cost-effectiveness ratio. Finally, we determined that the optimal numbers of follow-ups for the low-, medium-, and high-risk groups were 9, 10, and 13, respectively. The study demonstrates that the DP-based personalized follow-up strategy significantly improved the efficiency of recurrence detection and resource utilization in LAGC. These findings highlight the potential of DP algorithms in clinical decision-making and provide a foundation for future personalized follow-up studies.
Evidence on discordant familial cancer associations and their relevance in non-Western populations remains limited. This study assessed concordant and discordant cancer risks across major cancer sites in Korean women by comparing individuals with and without a family history of cancer. In total, 5,015,485 cancer-free women aged ≥ 40 years who participated in the national breast cancer screening program were included. Participants reported a family history of stomach, colorectal, liver, breast, cervical, or other cancers at screening. The risks of overall, site-specific, concordant (same cancer site as the family history), and discordant cancers (different cancer sites from the family history) were evaluated. Overall, a family history of any cancer was associated with a higher hazard of cancer (HR, 1.11; 95% CI, 1.10-1.12), with similar associations for cancers diagnosed before age 50 years (HR, 1.12; 95% CI, 1.09-1.14) and those diagnosed at age 50 years or older (HR, 1.13; 95% CI, 1.12-1.14). Elevated hazards associated with a family history were observed for most cancer sites, except for cervical, kidney, and brain cancers. Concordant associations were observed for gastric, colorectal, breast, and liver cancers (HRs, 1.36-2.43), whereas cervical cancer showed no significant concordant association. Modest but statistically significant discordant associations were observed across the five family history cancer types (HRs, 1.05-1.13). These associations were generally consistent across age groups. A family history of cancer was associated with both overall and site-specific cancer risk, with stronger associations for concordant cancers and more modest associations for discordant cancers.
All cases of invasive cervical cancer (ICC) and subsets of high-grade cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) and adenocarcinoma in situ (AIS) in Norway are tested for 37 human papillomavirus (HPV) genotypes, within a mandatory national surveillance system. We assessed the proportional attribution of HPV types in cervical lesions from predominantly unvaccinated women reported during 2017-2021 (baseline population) and the HPV type distribution by vaccination status in vaccine-eligible cases reported during 2017-2024. Among baseline CIN2/3 cases (n = 3087), 48% were attributable to HPV16/18, 28% to HPV31/33/45, 12% to HPV52/58 and 8% to other high-risk types (HPV35/39/51/56/59). For AIS (n = 550), almost all cases were attributed to HPV16/18 (91%) and HPV45 (6%). For ICC (n = 1265), 75% were attributable to HPV16/18, 15% to HPV31/33/45, 3% to HPV52/58 and 4% to other high-risk types. Among CIN2/3 cases born 1997 or later (eligible for vaccination at age 11-12 years, n = 154), HPV16-attribution was higher in unvaccinated cases (49.9%, 95% CI: 33.7-66.1) than in cases vaccinated before age 15 (1.1%, 95% CI: 0-3.4). In CIN2/3 cases born 1991-1996 (eligible for catch-up vaccination, n = 1541), HPV16-attribution was 45.7% (95% CI: 41.9-49.7) in unvaccinated versus 35.5% (95% CI: 32.5-38.6) in vaccinated cases. Minor differences by vaccination status were observed for catch-up-eligible AIS (n = 445) and ICC (n = 135) cases. In conclusion, the baseline genotype distribution in high-grade cervical lesions and ICC in Norway aligns with global data. Strong protection against HPV16-induced CIN2/3 was seen in women vaccinated before age 15 years.
Breast cancer progression varies across molecular subtypes, influencing detection rates and prognosis. Differences in the proportion of interval cancers (PIC)-cancers detected symptomatically between scheduled screening rounds-have been observed across subtypes, likely reflecting heterogeneity in tumour growth dynamics. We applied a continuous-growth natural history model to a cohort of 7818 breast cancer patients diagnosed between 2007 and 2020 in Sweden. Using subtype-specific estimates, we quantified the distributions of interval cancers within the 2-year period between screening rounds, differentiating by tumour sizes of missed interval cancers at their last negative screen. Additionally, the fitted model enabled estimation of subtype-specific tumour mean doubling times (MDT) and the average duration from tumour onset to symptomatic diagnosis. Triple-negative breast cancers (TNBC) exhibited the fastest growth (MDT: 126 days), followed by Luminal B-like (203 days) and Luminal A-like (332 days). Corresponding mean asymptomatic times (MAT) were 4.5, 7.6, and 11.8 years, respectively. Observed PICs among regular attenders were 48.9% (TNBC), 32.3% (Luminal B-like), and 22.0% (Luminal A-like), closely aligning with model-based expectations. Approximately 17% of TNBC interval cancers were estimated to have had diameters ≤ 1 mm at the last negative screen, versus 13% for Luminal B-like and 8% for Luminal A-like tumours. Our model integrates tumour growth into the detection processes to estimate subtype-specific tumour dynamics and their impact on the PIC. The results support the hypothesis that higher PICs in more aggressive subtypes are driven by faster tumour growth and shorter asymptomatic periods. Our results may inform screening strategies tailored to patients' risk.
Smoking and solid fuel are common exposures among Chinese adults, yet evidence regarding their associations with cancer mortality remains inconsistent, and their joint effects are insufficiently studied. Using data from the Pengzhou site of the China Kadoorie Biobank in Sichuan Province, we applied Cox proportional hazards models to examine associations of smoking, cooking fuel use, and co-exposure with mortality from overall cancer and major site-specific cancers. Among 55,404 participants, 61.63% were women, 75.15% reported cooking, and 46.38% reported smoking; 2030 cancer deaths occurred during follow-up. Current smoking and solid fuel cooking were associated with 27% and 18% higher risks of overall cancer mortality. Initiation before 18 years increased overall cancer mortality by 37%, esophageal cancer mortality by 107%, and lung cancer mortality by 86%. Higher daily cigarette consumption, longer smoking duration, and greater cumulative smoking were each positively associated with mortality from overall cancer, esophageal cancer, and lung cancer. Compared with individuals who neither smoked nor used solid fuels, solid fuel use alone increased overall cancer mortality by 24%, while smoking alone increased overall mortality by 32% and esophageal cancer mortality by 144%. Individuals exposed to both smoking and solid fuel use had higher mortality risks, reaching 49% for overall cancer, 198% for esophageal cancer, and 94% for lung cancer. These findings highlight the critical importance of quitting smoking and promoting clean cooking fuels for cancer prevention.
The incidence of anal cancer in older women has risen significantly in recent decades, yet no standard screening strategy exists. Screening aims to detect potentially precancerous lesions, anal intraepithelial neoplasia (AIN), which can be treated to prevent cancer progression. In this prospective study, we assessed the prevalence of high-risk human papillomavirus (hrHPV), abnormal anal cytology, and AIN confirmed by high-resolution anoscopy (HRA)-guided biopsy. Women aged ≥ 40 undergoing routine screening colonoscopy in Cologne, Germany, were enrolled. Before colonoscopy, anal samples were collected for hrHPV testing and cytology. Participants with positive hrHPV and/or abnormal cytology underwent HRA with biopsy and treatment if necessary. Among 483 women (November 2023-March 2025), hrHPV was detected in 78 (16.1%), while cytological abnormalities were found in only 6 (1.2%). In hrHPV-positive women, HRA identified low-grade squamous intraepithelial lesion (LSIL) in 11 (14.1%) and high-grade squamous intraepithelial lesion (HSIL) in 6 (7.7%); all lesions were treated with argon plasma coagulation. Anal symptoms (bleeding, pain, or pruritus) were associated with hrHPV positivity (adjusted PRR: 1.72; p = 0.023). Among hrHPV-positive participants, infection with multiple hrHPV types was linked to AIN (adjusted PRR: 2.90; p = 0.017). In conclusion, hrHPV prevalence was relatively high, while cytology alone showed limited sensitivity for detecting AIN. Identification and treatment of high-grade lesions, potentially precursors to anal cancer, suggest that screening could help prevent disease progression and support incorporating anal hrHPV testing into preventive strategies for women.
This study compared 25 sinonasal mucosal melanomas (SNMM) and 9 conjunctival melanomas (CM) using whole-exome and RNA sequencing. Median patient age was 64 years for SNMM and 54 years for CM. SNMM predominantly occurred in the nasal cavity (14/25, 56%) or both nasal cavity and paranasal sinuses (9/25, 36%). All CM cases were unilateral. NRAS mutations were found in 20% (5/25) of SNMM and 22% (2/9) of CM cases. RAS mutations were significantly associated with shorter progression-free survival in SNMM. BRAF mutations were detected in 22% (2/9) of CM cases (all V600E) and 8% (2/25) of SNMM cases (non-V600E). NF1 mutations occurred in 16% (4/25) of SNMM and 11% (1/9) of CM cases. Only one KIT mutation was found, in an SNMM case. Nearly all SNMM and CM cases exhibited alterations in the RTK-RAS signaling pathway. CM showed a higher frequency of UV-associated mutations than SNMM. RNA sequencing identified two novel gene fusions (PTPRK::PAX3 and GNA13::NF1) in SNMM. The most common tumor microenvironment subtype in both was D-type. SNMM had higher cancer-associated fibroblast infiltration but lower CD4+ T cell infiltration than CM. Among tumor suppressor genes, CDKN2B exhibited the highest frequency of biallelic inactivation in SNMM (5/25, 20%) and CM (1/6, 17%). Reactome pathway enrichment analysis revealed enrichment of cell cycle-related pathways in both tumor types. In conclusion, these findings delineate distinct genomic profiles of SNMM and CM, revealing significant pathogenic similarities, particularly the involvement of the RTK-RAS pathway and cell cycle-related pathways, despite potential differences in etiological factors.
Many real-world patients with advanced biliary tract cancer (BTC) are excluded by TOPAZ-1 criteria; this study assessed cisplatin and gemcitabine plus durvalumab (CGD) efficacy and safety in these patients. Data from 1358 patients with advanced BTC treated with first-line CGD across 55 international centers were retrospectively analyzed. Patients were classified as TOPAZ-1-in (meeting all inclusion criteria) or TOPAZ-1-out (meeting ≥ 1 exclusion criterion). Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Furthermore, OS and PFS of the TOPAZ-1-out cohort were compared with reconstructed survival data from the phase III trial. 912 (67.1%) patients were classified as TOPAZ-1-in, and 446 (32.9%) as TOPAZ-1-out. After a median follow-up of 14.5 months (95% CI: 13.7-36.5), OS was 16.1 months in TOPAZ-1-in and 12.5 months in TOPAZ-1-out (HR 0.69, 95% CI: 14.6-16.5, p = 0.0001); PFS was 8.2 versus 6.5 months (HR 0.73, 95% CI: 7.1-8.1, p < 0.0001). Median OS in the TOPAZ-1-out cohort (12.5 months) was nearly identical to the phase III trial experimental arm (12.9 months; HR 1.15, p = 0.13); for PFS the HR was 1.12 (95% CI 0.93-1.42; p = 0.09). Among TOPAZ-1-out patients, active infection, elevated bilirubin, and ECOG PS > 1 were linked to poorer OS, while no detrimental impact emerged for ALT/AST abnormalities, corticosteroid use, renal or hematologic parameters, or prior surgery within 6 months, suggesting treatment effectiveness was broadly maintained across clinical subgroups. Furthermore, TOPAZ-1-out patients experienced no significant increase in adverse events compared with the TOPAZ-1-in group. Real-world data suggest CGD may be effective in TOPAZ-1-out patients, with no evident increase in toxicity, supporting the potential expanded use of the regimen in clinical practice.
Esophageal adenocarcinoma (EAC) exhibits marked male predominance with male-to-female ratios reaching 8.5:1, yet the molecular basis underlying this sex disparity remains poorly characterized. We analyzed 92 EAC specimens using mass spectrometry-based proteomics, comprising 47 female and 45 male tumors from treatment-naïve patients. Differential expression, pathway enrichment, immunohistochemical, and survival analyses were used to identify sex-associated proteomic features and prognostic signatures. Proteomic profiling revealed focal yet biologically meaningful sex differences in EAC. After multiple testing correction, three proteins were differentially expressed: the autosomal protein pregnancy zone protein (PZP), enriched in female tumors, and the Y-chromosome-encoded proteins DDX3Y and RPS4Y1, which were overexpressed in male tumors. At nominal significance, proteins upregulated in female tumors showed marked enrichment of immune-related pathways. Proteins correlated with PZP expression formed a network dominated by complement cascade. Clinically, elevated PZP expression was associated with significantly poorer overall survival specifically in male patients, with no significant association detected in the combined or female-only cohort. Proteome-wide survival analyses further demonstrated distinct sex-specific prognostic landscapes. Our study provides the first comprehensive characterization of sex-associated proteomic differences in EAC. Sex shapes immune-related pathways, prognostic proteomic signatures, and survival associations. PZP emerges as a sex-differential, complement-associated protein with adverse prognostic significance in male patients, highlighting sex as a biologically and clinically relevant variable in EAC.
Although previous cohort studies have examined the association between vegetable and fruit intake and cancer risk, the findings remain inconsistent. Using data from 50,987 participants in the Shanghai Suburban Adult Cohort and Biobank (2016 to 2019), we investigated the relationship between vegetable and fruit intake and the incidence of cancers through linkage with the cancer registry up to June 30, 2024. Participants in the highest quartile of total vegetable and fruit intake had a lower risk of overall cancer (HR: 0.81, 95% CI: 0.72-0.90), with similar inverse associations observed for vegetables and fruits separately. Higher intake was also associated with lower risks of lung and stomach cancers, whereas no associations were observed for colorectal cancer. In continuous analyses, each SD increase in total vegetable and fruit intake was associated with a lower risk of overall cancer (HR: 0.92, 95% CI: 0.88-0.97), and the findings were generally consistent with those from quartile-based analyses. In subgroup analyses, these inverse associations were observed among participants with favorable lifestyles and health conditions. RCS analyses identified nonlinear associations between fruit intake and the risks of overall and lung cancer, with the protective associations becoming less pronounced at excessive intake levels.
We undertook a statistical modeling study to determine the effect of implementing population-based prostate-specific antigen (PSA) screening in England on overdiagnosis and PSA testing rates in comparison with the current opportunistic testing policy. Our model merged English data on life expectancy, rates of PSA testing and incidence of prostate cancer by stage with epidemiological data on lead time. In the base scenario, introduction of population-based screening led to an approximate 25% reduction in both PSA testing and overdiagnosis in the population compared with the current policy. This was due to the anticipated decrease in PSA testing and overdiagnosis in men aged 70+ years being larger than the projected increase in PSA testing and overdiagnosis in men 50-69 years. The overall incidence of early-stage prostate cancer was similar. Population-based screening was found to detect more early-stage cancers that were not overdiagnosed, and is therefore likely to have a greater impact on prostate-cancer mortality than current policy. Findings were robust in sensitivity analyses including an entirely independent modeling approach based on the UK Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP). In conclusion, opportunistic screening policies in England have led to high rates of overdiagnosis and PSA testing. A risk-adapted, population-based prostate cancer screening program would likely reduce the number of PSA tests and overdiagnoses, and increase benefits of PSA testing from reduced prostate-cancer mortality. Population health in England would be improved by adopting an organized PSA screening program and policies to reduce opportunistic PSA testing.
Adjuvant nivolumab is approved for esophageal or gastroesophageal junction cancer after neoadjuvant chemoradiotherapy and resection. In the CheckMate-577 trial, Grade 3-5 nivolumab-related adverse events (AEs) occurred in 5% of patients, with early discontinuation due to toxicity in 9%. However, real-world data on immunotherapy-related adverse events (irAEs) are limited. This study assessed the cumulative incidence of irAEs in a real-world setting. In this retrospective cohort study, all patients receiving ≥ 1 cycle of adjuvant nivolumab at three Dutch gastroesophageal cancer centers were included. Clinical data were extracted from electronic records. The primary outcome was the cumulative incidence of Grade 3-5 irAEs. Secondary outcomes included predictors, timing, and clinical outcomes of Grade 3-5 irAEs, and cumulative incidence of Grade 2 irAEs. Among 142 patients with median follow-up 27.9 months, Grade 3-5 irAEs occurred in 15%. Hepatitis (3%), pneumonitis (2%), and myocarditis (2%) were most common. Two fatal irAEs occurred (1%). Median time to first Grade 3-5 irAE was 2.0 months (IQR 0.7-6.4). Grade 3-5 irAEs led to hospitalization in 9%, required systemic corticosteroids in 11%, and resulted in clinical sequelae in 8%. No predictors for Grade 3-5 irAEs were identified. Early discontinuation due to any irAE occurred in 24%. In conclusion, severe irAEs (Grade 3-5) occurred more frequently than in CheckMate-577 and often required hospitalization and immunosuppression, with sequelae in a significant proportion. Discontinuation due to irAEs was higher than in CheckMate-577 (24% vs. 9%). Careful risk-benefit assessment and active monitoring during adjuvant nivolumab therapy are warranted.
Cancer survivors have an elevated risk of developing subsequent primary cancers, including colorectal cancer (CRC), and may benefit from tailored screening approaches to reduce incidence and morbidity. A retrospective cohort of adults diagnosed with cancer (excluding CRC) in Alberta, Canada from 2000 to 2021 who survived at least 6 months was used to investigate the incidence of CRC compared to the cancer-free population. Incidence rate differences and standardized incidence ratios (SIRs) were used to characterize risk across first primary cancer sites, sexes, age groups, and survivorship periods, as well as according to CRC stage, histology, and subsite. Multivariable Fine-Gray models were used to identify risk factors within site-specific survivorship groups. Among 172,928 cancer survivors, 1812 were diagnosed with CRC during a median follow-up of 4.9 years. Compared to the cancer-free population, survivors had an elevated risk of CRC (SIR = 1.26, 95% CI: 1.20-1.32). The risk of CRC varied across first primary cancer sites but remained elevated among both short- and long-term survivors. Cancer survivors were at an elevated risk of developing late stage (III/IV) CRC compared to the cancer-free population with the highest risk in the proximal colon and among long-term survivors (5+ years). Depending on the first primary cancer site, risk factors for subsequent CRC included older age at diagnosis, male sex, overweight/obese body mass index, earlier stage at diagnosis, and treatment type. These findings demonstrate the importance of improving adherence to CRC screening guidelines among cancer survivors. Greater research is needed to identify high-risk survivorship groups who may require enhanced screening.
Cancer survivors frequently experience cancer-related cognitive impairment (CRCI), but the contributions of different anti-cancer therapies remain unclear. Patients with breast or gynaecological cancer were recruited before any anti-cancer treatment. Cognitive function was assessed by objective and subjective measures pre-treatment (T0), post-treatment (T1), and 1 year after T1 (T2). Objective measures include Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test (TMT), Controlled Oral Word Association Test (COWA), and Mnemonic Similarity Task (MST). Subjective measures include Functional Assessment of Cancer Therapy-Cognitive scale (FACT-Cog) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Linear mixed models were performed. Patients (n = 234) were of age 55.4 ± 11.6 years. At T1, chemotherapy was associated with worse visual searching and motor speed (TMT-A: β = 0.36, 95% CI: 0.03-0.69), perceived global function (FACT-Cog Global Function: β = -0.39, 95% CI: -0.67 to -0.11), and cognitive function (EORTC QLQ-C30: β = -0.50, 95% CI: -0.82 to -0.18) compared to endocrine therapy. At T2, endocrine therapy was associated with poorer verbal learning and memory performance (HVLT-R total recall: β = -0.40, 95% CI: -6 to -0.03) and higher perceived cognitive impairments (FACT-Cog PCI: β = 0.34, 95% CI: 0.05-0.63). In conclusion, CRCI may occur during certain types of chemotherapy but appears to ameliorate over time. Ongoing endocrine therapy may have longer-lasting impact on cognitive function. Appropriate counselling for informed decision making and good supportive care is needed.
Women with estrogen receptor negative (ER-) contralateral breast cancer (CBC) are 50% more likely to die of CBC compared to women with estrogen receptor positive (ER+) CBC. We comprehensively investigated risk factors for ER subtype-specific CBC using the Women's Environmental Cancer and Radiation Epidemiology Study, a population-based, case-control study of 1521 CBC cases under age 55 years and 2212 individually matched unilateral breast cancer controls. Information about breast cancer risk factors and ER status was obtained by interview and medical record abstraction and common genetic variants with GWAS. Multivariable rate ratios and 95% confidence intervals were estimated using conditional logistic regression models, adjusting for known and suspected risk factors. Among 2800 women where the matched case had known ER CBC status, chemotherapy, hormone therapy, and increasing number of full-term pregnancies were associated with decreased ER+ CBC risk. Drinking, smoking, first breast cancer lobular histology, first-degree breast cancer family history, a polygenic risk score (PRS) of 313 common variants, and an ER+ subtype-specific PRS were associated with increased ER+ CBC risk. More than 2 years of breastfeeding was associated with decreased ER- CBC risk. While none of the PRSs were associated with ER- CBC risk, first- and second-degree family history of breast cancer and second-degree family history of ovarian cancer were associated with increased ER- CBC risk. We identified differential risk factors for ER subtype-specific CBC which can inform individualized risk prediction models for future clinical impact. There remains an unexplained genetic component of ER- CBC.
People with HIV (PWH) are living longer, but contemporary data on non-AIDS-defining cancers (NADCs) in Italy remain limited. We assessed incident cancers in a retrospective cohort of PWH in Milan, Italy, between January 2000 and December 2023. Follow-up was grouped into 2000-2007, 2008-2015, and 2016-2023. Incidence rates (IRs) were calculated per 100,000 person-years (PYs). Multivariable Poisson regression estimated adjusted (age, mode of HIV acquisition, and prior AIDS diagnosis) IR ratios (aIRRs) for first incident NADCs. Standardized incidence ratios (SIRs) compared observed cancers with expected cases in the general population. Among 4642 PWH contributing 50,086 PYs, 321 first incident NADCs were diagnosed. NADC incidence increased from 518 (95% CI 422-636) in 2000-2007 to 812 (95% CI 683-967) in 2016-2023. Non-virus-related cancer incidence increased from 293 to 582 per 100,000 PYs, whereas virus-related cancer incidence remained stable, from 225 to 230 per 100,000 PYs. People who inject drugs (PWID) versus heterosexuals (aIRR 1.71, 95% CI 1.33-2.20), and prior AIDS diagnosis (aIRR 1.33, 95% CI 1.05-1.69) were associated with higher NADC incidence. Compared with the general population, lung cancer incidence was increased in females (SIR 3.21, 95% CI 1.94-5.32). Anal cancer incidence was markedly elevated in both males and females (SIR 59.16, 95% CI 42.06-83.22 and 18.55, 95% CI 8.33-41.30, respectively). The excess cancer burden in this cohort was concentrated in selected NADCs, particularly anal cancer and, in females, lung cancer.
