Survival and degree of spread for female breast cancers in New South Wales from 1980 to 2003: implications for cancer control

This study investigated associations of degree of spread at diagnosis of breast cancer and socio-demographic factors with the risk of death among NSW females diagnosed in 1980–2003. Trends by diagnostic period, socio-demographic differences, and the implications for cancer control were considered. NSW Central Cancer Registry data were analyzed using regression and rank-order tests to show predictors of death from breast cancer and trends in degree of spread. Compared with localized disease, case fatality was thrice and 14 times higher for cancers with regional spread and distant metastases, respectively. After adjusting for degree of spread and socio-demographic differences, the relative risk of death from breast cancer has declined in recent diagnostic periods compared with the 1980–1983 baseline, reaching a low of 0.38 (0.35, 0.40) for 1999–2003. Age-specific analyses indicated that relative risks were lower in 1999–2003 for 50–69 year olds (RR = 0.31) than younger (RR = 0.40), or older (RR = 0.46) females. Regional or distant disease at diagnosis was lowest in the older age groups, the highest socio-economic stratum and in more recent periods. Females born in nonEnglish speaking countries presented with more advanced disease, as did metropolitan women with the highest access to health services. Degree of spread of cancer at diagnosis is a powerful predictor of case fatality. Case fatalities from breast cancer have declined by diagnostic period, after adjusting for degree of spread, which may reflect treatment and screening advances. Attention should be directed at reducing disparities by socio-economic status and encouraging migrant women to present earlier.     

Risk and Influencing Factors for Subsequent Primary Lung Cancer After Treatment of Breast Cancer: A Systematic Review and Two Meta-Analyses Based on Four Million Cases

IntroductionTo compare the risk of developing lung cancer between patients with breast cancer and the general population and explore the risk factors for the development of primary lung cancer after treatment for breast cancer.MethodsThe PubMed, EMBASE, and Web of Science databases were searched from the establishment date to October 11, 2020. Two separate meta-analyses were performed: one focused on studies reporting the risk of subsequent lung cancer after breast cancer and one focused on studies exploring the risk factors for subsequent lung cancer in patients with breast cancer. The standardized incidence ratios with 95% confidence intervals were combined to compare the risk of developing lung cancer between patients with breast cancer and the general population. The relative risks (RRs) or ORs with 95% confidence intervals were combined to assess the association of clinicopathological parameters with the risk of developing lung cancer after breast cancer. All statistical analyses were conducted by STATA 12.0.ResultsA total of 15 studies involving 1,161,979 patients were eventually included in the first meta-analysis, and the pooled results indicated that female patients with breast cancer revealed a significantly higher risk of developing subsequent lung cancer (standardized incidence ratio = 1.25, p < 0.001). In addition, a total of 22 articles involving 3,090,620 patients were included in the second meta-analysis. The pooled results indicated that smoking (OR = 9.73, p < 0.001) and radiotherapy (RR = 1.40, p < 0.001) were risk factors for developing subsequent lung cancer in patients with breast cancer, and chemotherapy (RR = 0.69, p = 0.002), positive estrogen receptor status (RR = 0.93, p = 0.014) and positive progesterone receptor status (RR = 0.86, p < 0.001) were protective factors. Meanwhile, subgroup analysis based on the relative position of the breast and lung cancers (ipsilateral versus contralateral) was conducted, which indicated that radiotherapy only increased the risk of ipsilateral lung cancer in patients with breast cancer (RR = 1.27, p = 0.001).ConclusionsPatients with breast cancer are more likely to develop lung cancer than the general population, and the risk of developing primary lung cancer after breast cancer is affected by smoking, radiotherapy, chemotherapy, estrogen receptor status and progesterone receptor status.     

Green tea, black tea consumption and risk of lung cancer: A meta-analysis

Studies investigating the association of green tea and black tea consumption with lung cancer risk have reported inconsistent findings. To provide a quantitative assessment of this association, we conducted a meta-analysis on the topic. Studies were identified by a literature search in PubMed from 1966 to November 2008 and by searching the reference lists of relevant studies. Summary relative risk (RR) estimates and their corresponding 95% confidence intervals (CIs) were calculated based on random-effects model. Our meta-analysis included 22 studies provided data on consumption of green tea or black tea, or both related to lung cancer risk. For green tea, the summary RR indicated a borderline significant association between highest green tea consumption and reduced risk of lung cancer (RR = 0.78, 95% CI = 0.61–1.00). Furthermore, an increase in green tea consumption of two cups/day was associated with an 18% decreased risk of developing lung cancer (RR = 0.82, 95% CI = 0.71–0.96). For black tea, no statistically significant association was observe through the meta-analysis (highest versus non/lowest, RR = 0.86, 95% CI = 0.70–1.05; an increment of two cups/day, RR = 0.82, 95% CI = 0.65–1.03). In conclusion, our data suggest that high or an increase in consumption of green tea but not black tea may be related to the reduction of lung cancer risk.     

Family history of malignancies and risk of breast cancer: prospective data from the Shanghai women’s health study

A population-based cohort study was conducted in Shanghai, China, to investigate the relationship between family cancer history in first-degree relatives and risk of breast cancer. A total of 570 newly diagnosed breast cancer patients were identified from the cohort of 73,222 women during the follow-up period. Breast cancer risk was elevated (RR = 1.74, 95% CI: 1.10–2.73) for those with a family history of breast cancer and the risk was stronger for women who were younger than 55 years (RR = 2.07, 95% CI: 1.17–3.64). In addition, a significantly increased risk was observed for women with a family history of leukemia (RR = 2.06; 95% CI: 1.02–4.15) and among younger women, those who reported having a family history of any cancer (RR = 1.41, 95% CI: 1.10–1.82), lung cancer (RR = 1.72, 95% CI: 1.12–2.65), and esophageal cancer (RR = 2.99, 95% CI: 1.62–5.51). This cohort study suggests that, as previously observed in high risk populations, family history plays an important role in breast cancer also in a low risk population. The link between breast cancer risk and family history of cancers of the lung and esophagus, as well as leukemia, warrants further investigation.     

Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies

Numbers of epidemiologic studies assessing soy consumption and risk of breast cancer have yielded inconsistent results. We aimed to examine the association between soy isoflavones consumption and risk of breast cancer incidence or recurrence, by conducting a meta-analysis of prospective studies. We searched for all relevant studies with a prospective design indexed in PUBMED through September 1st, 2010. Summary relative risks (RR) were calculated using fixed- or random-effects models. Pre-specified stratified analyses and dose–response analysis were also performed. We identified 4 studies of breast cancer recurrence and 14 studies of breast cancer incidence. Soy isoflavones consumption was inversely associated with risk of breast cancer incidence (RR = 0.89, 95% CI: 0.79–0.99). However, the protective effect of soy was only observed among studies conducted in Asian populations (RR = 0.76, 95% CI: 0.65–0.86) but not in Western populations (RR = 0.97, 95% CI: 0.87–1.06). Soy isoflavones intake was also inversely associated with risk of breast cancer recurrence (RR = 0.84, 95% CI: 0.70–0.99). Stratified analyses suggested that menopausal status may be an important effect modifier in these associations. We failed to identify a dose–response relationship between total isoflavones intake and risk of breast cancer incidence. Our study suggests soy isoflavones intake is associated with a significant reduced risk of breast cancer incidence in Asian populations, but not in Western populations. Further studies are warranted to confirm the finding of an inverse association of soy consumption with risk of breast cancer recurrence.     

Mouse mammary tumor like virus sequences in breast milk from healthy lactating women

Aspirin and other non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit aromatase activity and thus could selectively lower incidence of hormone receptor positive tumors. We assessed whether the association of aspirin and other NSAIDs with postmenopausal breast cancer risk differs by estrogen and progesterone receptor (ER and PR) status of the tumor. A population-based cohort of 26,580 postmenopausal women was linked to a SEER Cancer Registry to identify incident breast cancers. Regular use of aspirin and other NSAIDs was reported on a self-administered questionnaire mailed in 1992. Cox proportional hazards models were used to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs) of breast cancer incidence overall and by ER and PR status, adjusting for multiple breast cancer risk factors. Through 2005, 1,581 incident breast cancer cases were observed. Compared to aspirin never users, women who regularly consumed aspirin had a lower risk of breast cancer (RR = 0.80; 95% CI: 0.71–0.90), and there was evidence for lower risk with increasing frequency of use (RR = 0.71 for aspirin use 6 or more times/week vs. never use; P trend = 0.00001). Inverse associations for regular aspirin use were observed for ER+ (RR = 0.77; 95% CI 0.67–0.89), ER− (RR = 0.78; 95% CI 0.56–1.08), PR+ (RR = 0.79; 95% CI 0.68–0.92), and PR− (RR = 0.73; 95% CI 0.56–0.95) breast cancers. In contrast, use of other NSAIDs was not associated with breast cancer incidence overall (RR = 0.95, 95% CI: 0.85–1.07), or by ER or PR status. Aspirin, but not other NSAID use, was associated with about 20% lower risk of postmenopausal breast cancer and did not vary by ER or PR status of the tumor, suggesting that the hypothesized protective effects of aspirin may either be through cellular pathways independent of estrogen or progesterone signaling, or on tumor microenvironment.     

Meta-analysis of vitamin D, calcium and the prevention of breast cancer

Vitamin D and calcium intake have been suggested to have protective effects against breast cancer; however, the data have been inconclusive. The present meta-analysis examined the overall effects of vitamin D intake, circulating 25(OH)D and 1α,25(OH)₂D levels, and calcium intake on breast cancer risk. Data from 11 studies on vitamin D intake, 7 studies on circulating 25(OH)D levels, 3 studies of circulating 1α,25(OH)₂D levels, and 15 studies on calcium intake and breast cancer risk were included in this analysis. From the meta-analysis, there was a significant inverse relationship between vitamin D intake and breast cancer risk, with an overall relative risk (RR) of high versus low vitamin D intake for breast cancer of 0.91 (95% CI = 0.85–0.97). The highest quantile of circulating 25(OH)D was found to be associated with a 45% (OR = 0.55, 95% CI = 0.38–0.80) decrease in breast cancer when compared with the lowest quantile. No significant association for the circulating 1α,25(OH)₂D level and breast cancer was found (OR = 0.99, 95% CI = 0.68–1.44). For calcium, a 19% (RR = 0.81, 95% CI = 0.72–0.90) decrease in breast cancer risk was found for those with highest quantile of calcium intake compared to the lowest quantile. These results provide strong evidence that vitamin D and calcium have a chemopreventive effect against breast cancer.     

Meat consumption and risk of lung cancer: evidence from observational studies

BackgroundA number of epidemiological studies have reported inconsistent findings on the association between meat consumption and lung cancer.DesignWe therefore conducted a systematic review and meta-analysis to investigate the relationship between meat consumption and lung cancer risk in epidemiological studies.ResultsTwenty-three case–control and 11 cohort studies were included. All studies adjusted for smoking or conducted in never smokers. The summary relative risks (RRs) of lung cancer for the highest versus lowest intake categories were 1.35 (95% confidence interval (CI) 1.08–1.69) for total meat, 1.34 (95% CI 1.18–1.52) for red meat, and 1.06 (95% CI 0.90–1.25) for processed meat. An inverse association was found between poultry intake and lung cancer (RR = 0.91, 95% CI 0.85–0.97), but not for total white meat (RR = 1.06, 95% CI 0.82–1.37) or fish (RR = 1.01, 95% CI 0.96–1.07).ConclusionsThe relationship between meat intake and lung cancer risk appears to depend on the types of meat consumed. A high intake of red meat may increase the risk of lung cancer by about 35%, while a high intake of poultry decreases the risk by about 10%. More well-designed cohort studies on meat mutagens or heme iron, meat cooking preferences, and doneness level are needed to fully characterize this meat–lung cancer association.     

Methylation scores for smoking,alcohol consumption and body mass index and risk of seven types of cancer

Methylation marks of exposure to health risk factors may be useful markers of cancer risk as they might better capture current and past exposures than questionnaires, and reflect different individual responses to exposure. We used data from seven case-control studies nested within the Melbourne Collaborative Cohort Study of blood DNA methylation and risk of colorectal, gastric, kidney, lung, prostate and urothelial cancer, and B-cell lymphoma (N cases = 3123). Methylation scores (MS) for smoking, body mass index (BMI), and alcohol consumption were calculated based on published data as weighted averages of methylation values. Rate ratios (RR) and 95% confidence intervals for association with cancer risk were estimated using conditional logistic regression and expressed per SD increase of the MS, with and without adjustment for health-related confounders. The contribution of MS to discriminate cases from controls was evaluated using the area under the curve (AUC). After confounder adjustment, we observed: large associations (RR = 1.5-1.7) with lung cancer risk for smoking MS; moderate associations (RR = 1.2-1.3) with urothelial cancer risk for smoking MS and with mature B-cell neoplasm risk for BMI and alcohol MS; moderate to small associations (RR = 1.1-1.2) for BMI and alcohol MS with several cancer types and cancer overall. Generally small AUC increases were observed after inclusion of several MS in the same model (colorectal, gastric, kidney, urothelial cancers: +3%; lung cancer: +7%; B-cell neoplasms: +8%). Methylation scores for smoking, BMI and alcohol consumption show independent associations with cancer risk, and may provide some improvements in risk prediction.     

Dietary Patterns and Risk of Invasive Ductal and Lobular Breast Carcinomas: A Systematic Review and Meta-analysis

The histopathologic subtypes of breast cancer, including invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), differ in terms of risk factors, progression, and response to treatment. The PubMed/Medline, Web of Science, and Scopus databases were searched up to February 2020 for published studies on the association between dietary patterns (Western diet [WD] or Mediterranean diet [WD]) and the risk of IDC/ILC of breast. Multivariable adjusted relative risk (RR) and 95% confidence intervals (CIs) comparing the highest and lowest categories of WD and MD patterns were combined by using the random-effects meta-analyses. After searching the databases, 10 eligible studies on the association of diet and IDC (7 articles) and ILC (3 articles) were included in the analysis. A statistically significant adverse association was observed between MD and IDC in case–control studies (RR = 0.47; 95% CI, 0.39-0.55; I² = 85.1%; P < .001). However, the association was nonsignificant in cohort studies (RR = 0.98; 95% CI, 0.92-1.05; I² = 88.8%; P = .003). The pooled analysis also suggested a significant and direct association between the WD and the risk of IDC (RR = 1.36; 95% CI, 1.18-1.53; I² = 63.7%; P = .017). The risk of ILC for the highest compared to the lowest category of MD was highly protective (RR = 0.76; 95% CI, 0.64-0.87; I² = 89.2%; P < .001), and a marginally significant association was found between the WD and risk of ILC (RR = 1.45; 95% CI, 1.04-1.86), with no heterogeneity (I² = 0; P = .52). This meta-analysis provides supporting evidence for the association between MD decreased risk of IDC and ILC of the breast and the association between WD and increased risk of IDC and ILC. Further investigations are needed to better understand the reasons behind the etiologic mechanisms of how dietary patterns affect patients differently by common breast cancer subtypes, including IDC and ILC.     

Risk of breast cancer in families of multiple affected women and men

Family history of first and second-degree relatives is known to increase the risk for breast cancer. Less data are available on the risks between defined multiple affected close and distant relatives for which the reliability of data may be an issue. Data on affected males are sparse. These questions and the probable genetic models were addressed in this study by means of a nationwide Swedish Family-Cancer Database. We estimated the effect of family history of breast cancer by Poisson regression for women of at least 30 years of age after adjusting for age, period, region, socioeconomic status, number of children, and age at first birth. The results of the study showed that relative risk (RR) for breast cancer was associated with a first degree as well as second-degree family history. Having at least two female affected first-degree relatives increased the RR at least to 2.8, favoring an additive interaction. The risk was increased around ten times in women with both parents affected. When either a father or a mother was affected, the RRs were nearly identical (RR = 1.73 and 1.74, respectively). The RR for a woman increased more when a brother was affected (RR = 2.48) compared to when a sister was affected (RR = 1.87). Having an affected grandmother showed lower familial excess risks than having an affected half sister (RR = 1.27, and 1.26; and RR = 1.39, and 1.50; respectively, for maternal and paternal relatives). We concluded that when both parents were diagnosed with breast cancer, the risk for the daughter was increased tenfold. Having an affected brother showed a somewhat higher risk than having an affected sister. The data suggest that male breast cancer has a higher genetic basis than female breast cancer, which invites further search of the underlying mechanisms.     

Socioeconomic differences in lung cancer incidence: a systematic review and meta-analysis

Objective  To investigate the associations between various socioeconomic indicators and lung cancer incidence. Methods  We searched PubMed and EMBASE databases for studies on socioeconomic position (SEP) and lung cancer incidence published through October 2007. Random-effect model was used to pool the risk estimates from the individual studies. We stratified the analysis by adjustment strategy to investigate the influence of smoking on socioeconomic gradient in lung cancer incidence. Results  Out of 3,288 citations, we identified 64 studies eligible for inclusion. Compared to the highest SEP level, we observed an overall increased risk in lung cancer incidence among people with low educational SEP (61%), low occupational SEP (48%), and low income-based SEP (37%). The negative social gradient for lung cancer incidence remained for most of the possible sets of pooled estimates obtained in subgroup analyses for occupational and educational SEP with less consistency for SEP based on income in studies adjusted and unadjusted for smoking. No evidence of publication bias was apparent. Conclusion  Lung cancer incidence was associated with low educational, occupational, and income-based SEP. The association, adjusted or unadjusted for smoking, points out the importance of social position to be addressed in all discussions on cancer preventive measures. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. This work was performed in the Department of Public Health Sciences, Division of Social Medicine/Epidemiology, Karolinska Institutet, Stockholm, Sweden.     

The association of atopic diseases with breast, prostate, and colorectal cancers: a meta-analysis

There is a long-standing interest in finding whether allergic disorders cause or prevent cancer. We meta-analyzed associations of allergies with prostate, breast, and colorectal cancers. We searched MEDLINE, EMBASE, and Web of Science between 1966 and 2008 and eligible reference lists. A total of 16 observational studies were included. Meta-analyses revealed no evidence that asthma, hay fever, or ‘any allergy’ are associated with cancers of the breast (relative risk, RR = 0.93, 95% CI: 0.73–1.19 for asthma; 1.04, 0.94–1.16 for hay fever; 1.01, 0.94–1.08 for any allergy); prostate (RR = 0.93, 95% CI: 0.76–1.15 for asthma; 0.96, 0.87–1.05 for hay fever; 1.01, 0.87–1.17 for any allergy); or colorectum (RR = 0.95, 95% CI: 0.77–1.16 for asthma; 0.95, 0.86–1.05 for hay fever; 0.94, 0.85–1.04 for any allergy). There was a positive association of atopy (assessed by allergen-specific IgE or skin prick testing) with prostate cancer (RR = 1.43, 95% CI: 1.08–1.91), but not breast (1.18, 0.90–1.55) or colorectal (1.32, 0.69–2.53) cancers. There is little epidemiological support for the immune surveillance theory or antigenic stimulation theory in breast or colorectal carcinogenesis. The findings for prostate cancer warrant further investigation.     

Intake of antioxidant nutrients and the risk of skin cancer

To investigate the associations between intake of antioxidant nutrients and risk of basal cell (BCC) and squamous cell carcinomas (SCC) of the skin, we carried out a prospective study among 1001 randomly selected adults living in an Australian community. Intake of antioxidants was estimated in 1996. Incident, histologically-confirmed BCC and SCC were recorded between 1996 and 2004. High dietary intake of lutein and zeaxanthin was associated with a reduced incidence of SCC in persons who had a history of skin cancer at baseline (highest versus lowest tertile, multivariable adjusted relative risk (RR) = 0.47, 95% confidence interval (CI): 0.25–0.89; P for trend = 0.02). In persons without a history of skin cancer at baseline, development of BCC was positively associated with intake of vitamins C and E from foods plus supplements (RR = 3.1, 95% CI: 1.1–8.6; P for trend = 0.03 and RR = 2.6, 95% CI: 1.1–6.3; P for trend = 0.02, respectively). In those with a skin cancer history at baseline, dietary intake in the second tertile for β-carotene (multivariable adjusted RR = 2.2, 95% CI: 1.2–4.1) and for vitamin E (multivariable adjusted RR = 2.1, 95% CI: 1.1–3.9) was associated with increased BCC risk, with no trend, and similar results were seen in those with a specific history of BCC. These data suggest quite different associations between antioxidant intake and SCC compared with BCC, consistent with other evidence of their different causal pathways.     

Breast cancer incidence and case fatality among 4.7 million women in relation to social and ethnic background: a population-based cohort study

Introduction  

Incidence of breast cancer is increasing around the world and it is still the leading cause of cancer mortality in low- and middle-income countries. We utilized Swedish nationwide registers to study breast cancer incidence and case fatality to disentangle the effect of socioeconomic position (SEP) and immigration from the trends in native Swedes.     

Fruit and vegetable consumption and incident breast cancer: a systematic review and meta-analysis of prospective studies

Background We conducted a systematic review and meta-analysis of prospective studies to clarify the relation of fruit and vegetable consumption with incident breast cancer.Methods We searched systematically PubMed and EMBASE databases up to November 2020 to include prospective studies that reported the association of fruit and vegetable consumption with incident breast cancer. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for the highest versus the lowest category of total fruit and vegetable, total fruit and total vegetable consumption, as well as fruit juice and subgroups of vegetables in relation to breast cancer incidence, using a random-effect model.Results Total fruit and vegetable consumption was associated with lower overall (RR = 0.91, 95% CI = 0.87–0.95) and postmenopausal breast cancer risk (RR = 0.88, 95% CI = 0.79–0.99). Total fruit consumption was associated with lower overall (RR = 0.93, 95% CI = 0.88–0.99) and postmenopausal breast cancer risk (RR = 0.93, 95% CI = 0.87–0.99). Total fruit and vegetable intake were associated with 11% and 26% lower risk of oestrogen- and progesterone-receptor-positive (ER+/PR+) and -negative (ER−/PR−) breast cancer, respectively. Total vegetable consumption was associated with 27% lower risk of ER−/PR− breast cancer. Fruit juice consumption was associated with increased overall breast cancer risk (RR = 1.04, 95% CI = 1.01–1.07). We did not find significant associations for subgroups of vegetable intake and breast cancer risk.Conclusions These findings suggest that high total fruit and vegetable consumption are associated with reduced risk of overall, postmenopausal, ER+/PR+ and ER−/PR− breast cancer.Subject terms: Risk factors, Breast cancer     

Carotenoids and breast cancer risk: a meta-analysis and meta-regression

The purpose of this article is to comprehensively summarize the associations between carotenoids and breast cancer and quantitatively estimate their dose–response relationships. We searched PubMed, Embase, and Cochrane databases (from January 1982 to 1 May 2011) and the references of the relevant articles in English with sufficient information to estimate relative risk or odds ratio and the 95% confidence intervals, and comparable categories of carotenoids. Two reviewers independently extracted data using a standardized form; with any discrepancy adjudicated by the third reviewer. 33 studies met the inclusion criteria. Comparing the highest with the lowest intake: dietary α-carotene intake significantly reduced the breast cancer risk by 9.0% (pooled RR = 0.91; 95% CI: 0.85–0.98; P = 0.01), dietary β-carotene intake reduced the risk by 6.0% (pooled RR = 0.94; 95% CI: 0.88–1.00; P = 0.05); total β-carotene intake reduced the risk by 5.0% (pooled RR = 0.95; 95% CI: 0.90–1.01; P = 0.08) when data from cohort studies were pooled. Significant dose–response relationships were observed in both the higher intake of dietary and total β-carotene with reduced breast cancer risk when data from cohort studies (P _trend < 0.01, P _trend = 0.03) and case–control studies (P _trend < 0.01, P _trend < 0.01) were pooled, respectively. Dietary α-carotene intake could reduce the breast cancer risk. The relationships between dietary and total β-carotene intake and breast cancer need to be confirmed. No significant association between dietary intake of β-cryptoxanthin, lutein/+zeaxanthin, and lycopene and breast cancer was observed.     

Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor

BackgroundDermatologic adverse events (AEs) are some of the most frequently observed toxicities of immune-checkpoint inhibitor therapy, but they have received little attention. The drugs, pembrolizumab and nivolumab are recently approved inhibitors of the programmed death (PD)-1 receptor that have overlapping AE profiles however, the incidence, relative risk (RR), and clinico-morphological pattern of the associated dermatologic AEs are not known.MethodsWe conducted a systematic review of the literature, and performed a meta-analysis of dermatologic AEs observed with the use of pembrolizumab and nivolumab in cancer patients. An electronic search was conducted using the PubMed, and Web of Science, and on the American Society of Clinical Oncology and European Society for Medical Oncology meeting abstracts' libraries for potentially relevant oncology trials, that employed the drugs at Food and Drug Administration-approved doses and reported dermatologic AEs. The incidence, RR and 95% confidence intervals were calculated using either random- or fixed-effects models based on the heterogeneity of included studies. The clinical presentation, histology of affected skin areas, and management strategies (based on institutional experience), are also presented.ResultsRash, pruritus and vitiligo were found to be the most frequently reported dermatologic AEs. The calculated incidence of all-grade rash with pembrolizumab and nivolumab was 16.7% (RR = 2.6) and 14.3% (RR = 2.5), respectively. Other significant all-grade AEs included pruritus (pembrolizumab: incidence, 20.2% [RR = 49.9]; nivolumab: incidence, 13.2% [RR = 34.5]) and vitiligo (pembrolizumab: incidence, 8.3% [RR = 17.5]; nivolumab: 7.5% [RR = 14.6]). Interestingly, all the vitiligo events were reported in trials investigating melanoma. The RR for developing dermatologic AEs in general, was 2.95 with pembrolizumab, and 2.3 with nivolumab.ConclusionWe found that pembrolizumab and nivolumab are both associated with dermatologic AEs, primarily low-grade rash, pruritus, and vitiligo, which are reminiscent of those seen with ipilimumab. Knowledge of these findings is critical for optimal care, maintaining dose intensity, and health-related quality of life in cancer patients receiving PD-1 inhibitors.