Melanoma In Women Research Articles

A Post-Pandemic Surge of Thick Melanomas in Women: A Nationwide Study on Skin Cancer Incidence During COVID-19

A Post-Pandemic Surge of Thick Melanomas in Women: A Nationwide Study on Skin Cancer Incidence During COVID-19

Synchronous double primary vulvar melanoma: a not so rare possibility. A clinical and dermoscopic case study.

Vulvar melanoma is considered rare, but it is the second most frequent vulvar neoplasm; 2% of melanomas in women arise in the vulvar area. It is important to highlight how the characteristics of vulvar melanoma differentiate it from classic cutaneous melanoma. Vulvar melanoma has different risk factors and clinical and dermoscopic characteristics; moreover, it has a higher recurrence rate and a greater likelihood of multifocality. Here, we present a case of a 44-year-old patient with two primary vulvar melanomas located on opposite sides of her vulva. The lesions were both flat, but they had distinct clinical and dermoscopic appearances. Melanoma of the genital tract is likely the result of a multifocal disorder of the melanocytes within the mucosa that inhabit the perineal squamous epithelium. The risk factors of vulvar melanoma differ from those of classical cutaneous melanomas. Vulvar melanoma occurs in an area shielded from ultraviolet radiation; the primary risk factors include chronic inflammatory disease, genetic susceptibility, irritant agents and viral infections. This case study reveals how a close examination of the genital area is important and how dermoscopy can aid in the differential diagnosis of vulvar lesions. Inspections of the genital area should be particularly thorough if a melanoma is detected there, given the higher risk of multifocality in that part of the body.

Exploratory profiles of phenols, parabens, and per- and poly-fluoroalkyl substances among NHANES study participants in association with previous cancer diagnoses

BackgroundSome hormonally active cancers have low survival rates, but a large proportion of their incidence remains unexplained. Endocrine disrupting chemicals may affect hormone pathways in the pathology of these cancers.ObjectiveTo evaluate cross-sectional associations between per- and polyfluoroalkyl substances (PFAS), phenols, and parabens and self-reported previous cancer diagnoses in the National Health and Nutrition Examination Survey (NHANES).MethodsWe extracted concentrations of 7 PFAS and 12 phenols/parabens and self-reported diagnoses of melanoma and cancers of the thyroid, breast, ovary, uterus, and prostate in men and women (≥20 years). Associations between previous cancer diagnoses and an interquartile range increase in exposure biomarkers were evaluated using logistic regression models adjusted for key covariates. We conceptualized race as social construct proxy of structural social factors and examined associations in non-Hispanic Black, Mexican American, and other Hispanic participants separately compared to White participants.ResultsPrevious melanoma in women was associated with higher PFDE (OR:2.07, 95% CI: 1.25, 3.43), PFNA (OR:1.72, 95% CI: 1.09, 2.73), PFUA (OR:1.76, 95% CI: 1.07, 2.89), BP3 (OR: 1.81, 95% CI: 1.10, 2.96), DCP25 (OR: 2.41, 95% CI: 1.22, 4.76), and DCP24 (OR: 1.85, 95% CI: 1.05, 3.26). Previous ovarian cancer was associated with higher DCP25 (OR: 2.80, 95% CI: 1.08, 7.27), BPA (OR: 1.93, 95% CI: 1.11, 3.35) and BP3 (OR: 1.76, 95% CI: 1.00, 3.09). Previous uterine cancer was associated with increased PFNA (OR: 1.55, 95% CI: 1.03, 2.34), while higher ethyl paraben was inversely associated (OR: 0.31, 95% CI: 0.12, 0.85). Various PFAS were associated with previous ovarian and uterine cancers in White women, while MPAH or BPF was associated with previous breast cancer among non-White women.Impact StatementBiomarkers across all exposure categories (phenols, parabens, and per- and poly- fluoroalkyl substances) were cross-sectionally associated with increased odds of previous melanoma diagnoses in women, and increased odds of previous ovarian cancer was associated with several phenols and parabens. Some associations differed by racial group, which is particularly impactful given the established racial disparities in distributions of exposure to these chemicals. This is the first epidemiological study to investigate exposure to phenols in relation to previous cancer diagnoses, and the first NHANES study to explore racial/ethnic disparities in associations between environmental phenol, paraben, and PFAS exposures and historical cancer diagnosis.

Melanoma predilection for the lower limbs of women compared with men.

The lower limb is a common site for melanoma in women, but the reason for this is not fully understood. To investigate this phenomenon in more detail, we assessed the specific subsites of primary melanoma occurring on the lower limbs of females compared with males across age groups. In a records-based study at an oncology hospital in north-west of England, among an unselected sample of patients with primary invasive melanoma treated between 2002-2015, information was collected on patient age at diagnosis, sex, and co-morbidities, and the tumor thickness and anatomical subsite (thigh, lower leg, foot for lower limb). Of a total sample of 1,522 patients, 316 (227, 72% female) had lower limb melanoma. The most common subsite was lower leg (142 cases with F:M ratio =3.74), followed by thigh (55 cases with F:M = 1.83) and feet (30 cases with F:M = 1.15). At ages<40 years the odds of thigh to foot melanoma was 20 times higher in females than in males (OR 20.0, 95% CI 2.6-152.6) and 7.5 times higher on the lower limb (OR 7.5, 95% CI 1.1-49.2). For ages 40+ years, the odds of females developing thigh melanoma compared to foot melanoma was similar in males versus females (OR 0.8), while the corresponding odds of lower leg melanoma in females versus males remained significantly increased at ages 40-59 and 60+ (OR 4.2 and 2.8 respectively). Our study demonstrates the female predilection for lower limb melanoma persists over most but not all subsites.However, there is heterogeneity in the female to male occurence of lower limb melanoma across subsites and at different ages, which may be linked to relative influence of genetic and environmental risk factors.

Exogenous Hormone Factors in Relation to the Risk of Malignant Melanoma in Women: A Systematic Review and Meta-Analysis.

Simple SummaryMany epidemiological studies have examined the relationship between cutaneous malignant melanoma (CMM) and both endogenous oestrogen exposure (e.g., age at menarche and parity) and exogenous hormone use (e.g., oral contraceptives (OCs) and menopausal hormone therapy (MHT)). Though a previous meta-analysis investigating the relationship between characteristics of female endocrine status and CMM risk found no significant association, the potential role of THERAPY AS oral contraceptive (OC) and hormonal replacement therapy (MHT) use still remains controversial. Since then, several studies have been published about the therapy with contrasting results, while CMM incidence continues to increase with a significant gender divergence. The therapy of OC and MHT may play a role in CMM and the removal of this could be useful as emerging therapeutics in melanoma. Therefore, we conducted this systematic review and meta-analysis to summarize the evidence and derive a more accurate estimation of exogenous hormone factors in women and CMM.The influence of exogenous female hormones on the risk of developing malignant melanoma in women remains controversial. The aim of our review and meta-analysis is to summarize the evidence and derive a more accurate estimation of the association between oral contraceptives (OCs) or menopausal hormone therapy (MHT) and the risk of developing malignant melanoma in women. PubMed, Web of Science, and Scopus database were searched for studies published up until October 2021. The PRISMA statement and MOOSE guidelines were followed. Studies were pooled using a random effects model. Heterogeneity was explored with the chi-square-based Cochran’s Q statistic and the I2 statistic. Publication bias was assessed with Begg’s test and Egger’s test. Forty-six studies met the eligibility criteria. The pooled analysis (26 studies) on OC use and the risk of developing cutaneous malignant melanoma (CMM) showed no significant association, but demonstrated significant association for cohort studies (OR 1.08, 95% CI 1.01–1.16; I2 = 0.00%, p = 0.544). The pooled analysis (16 studies) showed a significantly increased risk of CMM in association with MHT (OR 1.15, 95% CI 1.08–1.23; I2 = 25.32%, p = 0.169). Stratifying the results by study design showed that a significant increased risk of CMM was associated with MHT in the cohort studies (OR 1.12; 95% CI 1.04–1.19; I2 = 0%, p = 0.467). No significant publication bias could be detected. Further studies are needed to investigate the potential association with formulation, duration of use, and dosage of use, and to better understand the role of possible confounders.

Cancer in the Faroe Islands from 1960-2019 – incidence, mortality, and comparisons with the other Nordic countries

Purpose: In this paper, we present age-standardized cancer incidence and mortality rates in the Faroe Islands. We also compare with the Nordic rates and show incidence rate ratios (IRR) and mortality rate ratios (MRR). Materials and methods: The Faroese cancer registry (FCR) was established in 1994, with incidence available from 1960 and mortality from 1983. The FCR is a part of the NORDCAN collaboration, where the different Nordic countries all report anonymized cancer data by standardized methods, ensuring comparability. Validation efforts revealed that 13% of cases had not been reported to the FCR from 2006 to 2019, emphasizing the need for continued validation efforts of cancer registries. After validation, we submitted the updated cancer cases to NORDCAN and now present this data, taken directly from the NORDCAN website (2019 data). Results: We found that the incidence of the summary group all cancers in the Faroe Islands increased from 1960 to 2019, while cancer mortality decreased from 1983 to 2019. Comparisons with Nordic rates showed significantly lower IRRs for cancer in all cancers, bladder and urinary tract, and skin cancer for both sexes, while IRR was lower for breast cancer in women and prostate cancer in men. Contrary, IRR was higher for rectum and kidney cancer in women and esophagus and testicular cancer in men. There was an increased MRR for cancer in female organs, bladder and urinary tract, and kidney cancer in women, and esophagus and pancreas cancer in men. In contrast, malignant hematopoietic diseases and melanoma in women had a lower MRR. Conclusions: Cancer incidence in the Faroe Islands was lower than in the other Nordic countries. Of particular interest, the incidence of testicular cancer saw a steep increase during the last 20 years, and an investigation into possible causes for this is needed.

Reproductive factors, hormone use, and incidence of melanoma in a cohort of US Radiologic Technologists.

Are reproductive factors and exogenous hormone use associated with incidence of cutaneous melanoma while accounting for ultraviolet radiation (UVR) exposure across different life periods and sun sensitivity factors? Earlier age at menarche and late age at first birth, but not other estrogen-related factors were associated with an increased incidence rate of melanoma, with higher risks observed for earlier age at menarche and light hair color at age 15 years. Although estrogens have been recognized as photosensitizing, previous studies have reported inconsistent findings for the association of melanoma with estrogen-related factors. Most have not collected detailed skin cancer risk factors and have not thoroughly investigated effect modification by ambient UVR and sun sensitivity. Participants in the US Radiologic Technologists study, an occupational cohort of 146 022 radiologic technologists (73% women), were included and followed during the four time periods (1983-1989, 1994-1998, 2003-2005 and 2012-2014). Non-Hispanic white female participants who completed both the second (baseline) and third questionnaires, and did not report having cancer (except keratinocyte carcinoma) at baseline, were included and followed from their age at completion of the second (baseline) questionnaire until the earlier of first primary cancer diagnosis, including invasive melanoma of the skin, or completion of either the third or fourth questionnaire. Reproductive and exogenous hormonal factors were ascertained from the second (baseline) questionnaire, which also collected information on demographic, lifestyle factors and sun sensitivity factors. Ambient UVR was assigned by linking geocoded residential locations, based on self-reported residential history information collected from the third questionnaire to satellite-based ambient UVR data from the National Aeronautics and Space Administration's Total Ozone Mapping Spectrometer database. To examine the association of reproductive factors, exogenous hormone use, and first primary invasive melanoma of the skin, we used Poisson regression to calculate rate ratios (RRs) and 95% likelihood-based CIs, adjusting for attained age, birth cohort, lifetime average annual ambient UVR, contraceptives and menopausal hormone therapy use. To address the effect modification of ambient UVR exposure and sun sensitivities on melanoma risk, we conducted likelihood-ratio tests for multiplicative interaction. Over a median follow-up time of 17.1 years, 0.95% of eligible participants had an incident first primary melanoma (n = 444). Higher melanoma incidence rates were observed in participants with older attained age, blue/green/gray eye color, blonde/red/auburn natural hair color at age 15, fair skin complexion, and higher UVR. We found an increased incidence rate of melanoma in women who experienced menarche at an earlier age (13, 12 and <12 years vs ≥14 years: RR = 1.48, 95% CI = 1.11-1.98; 1.19, 0.89-1.61; 1.26, 0.93-1.73), and in women with older age at first birth (25-29 and ≥30 years vs <25 years; 1.09, 0.86-1.39; 1.48, 1.12-1.95; P-value for trend = 0.006). However, no significant association was observed for other reproductive factors, and for all exogenous hormone use. The associations of melanoma incidence for most reproductive factors and exogenous hormone use were not modified by ambient UVR, eye color, natural hair color at age 15 and skin complexion. The exception was that natural hair color at age 15 modified the associations of melanoma for age at menarche (P-value for interaction = 0.004) and age at first birth among parous women (0.005). In participants with blonde/red/auburn natural hair color at age 15, we found increased risk of melanoma among women who experienced menarche at age 13, 12 and <12 years (vs ≥14 years: RR = 3.54, 95% CI = 1.98-6.90; 2.51, 1.37-4.98; 2.66, 1.41-5.36, respectively; P-value for trend = 0.10). However, the association between age at menarche and melanoma was null in participants with brown/black natural hair color at age 15. Information on reproductive history and exogenous hormone use was self-reported. We did not have information on specific doses or formulations of exogenous hormone medications or breastfeeding. Women residing in areas of high ambient UVR and those with blonde/red/auburn natural hair color may constitute an additional high-risk group in need of more frequent skin cancer screening. Identifying susceptible periods of exposure or factors that modify UVR susceptibility may aid in guiding more targeted guidelines for melanoma prevention. This research was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services. Authors declare no conflict of interest. N/A.

An Observational Study on the Molecular Profiling of Primary Melanomas Reveals a Progression Dependence on Mitochondrial Activation.

Simple SummaryMalignant melanoma is the deadliest among the skin cancers. In the advanced stage, it shows extremely poor prognosis. The incidence and mortality of melanoma has been continuously increasing worldwide, primarily among the fair-skinned populations. To date, the best indicator for progression is the tumor thickness (Breslow). In this sense, there is a fundamental need to discover early indicators of disease progression. We believe that in-depth molecular profiling at the multiomic level of primary melanomas may find a signature that predicts disease progression toward metastasis. Here we report an observational study of a small primary melanoma cohort, in which in-depth molecular profiling was performed at the levels of protein expression, phosphorylation, and lysine acetylation. Our results provided evidence for dysregulation of pathways and biological processes at all molecular levels evaluated, in primary tumors from patients that ultimately developed a metastatic disease. Moreover, we provided evidence at the molecular level of the sex-related differences in the melanoma disease presentation.Melanoma in advanced stages is one of the most aggressive tumors and the deadliest of skin cancers. To date, the histopathological staging focuses on tumor thickness, and clinical staging is a major estimate of the clinical behavior of primary melanoma. Here we report on an observational study with in-depth molecular profiling at the protein level including post-translational modifications (PTMs) on eleven primary tumors from melanoma patients. Global proteomics, phosphoproteomics, and acetylomics were performed on each sample. We observed an up-regulation of key mitochondrial functions, including the mitochondrial translation machinery and the down-regulation of structural proteins involved in cell adhesion, the cytoskeleton organization, and epidermis development, which dictates the progression of the disease. Additionally, the PTM level pathways related to RNA processing and transport, as well as chromatin organization, were dysregulated in relation to the progression of melanoma. Most of the pathways dysregulated in this cohort were enriched in genes differentially expressed at the transcript level when similar groups are compared or metastasis to primary melanomas. At the genome level, we found significant differences in the mutation profiles between metastatic and primary melanomas. Our findings also highlighted sex-related differences in the molecular profiles. Remarkably, primary melanomas in women showed higher levels of antigen processing and presentation, and activation of the immune system response. Our results provide novel insights, relevant for developing personalized precision treatments for melanoma patients.

Hormone therapy and melanoma in women.

Although primary cutaneous melanoma accounts for approximately 3% of all malignant skin tumors, it has the greatest contribution to skin cancer-related death. Sex-specific differences in melanoma tumor behavior have been described, and melanoma pathogenesis may be hormonally mediated. This review aims to summarize the literature to date regarding the effects of hormone therapy on melanoma in women. Women's exogenous hormone use has changed dramatically over the past few decades. Thus, we focus on studies investigating the associations between oral contraception, fertility treatments, menopausal hormone therapy (MHT), and melanoma. Across hormone therapy types, there does not appear to be a well-established association between exogenous female hormones and melanoma incidence. However, MHT practices and formulations vary significantly across countries. Although MHT does not appear to increase melanoma risk in studies from the United States, conflicting results have been observed in Europe. Unopposed estrogen MHT formulations require further investigation to determine a clear pattern between hormone use and the development of melanoma.

Vulvar Melanoma: Molecular Characteristics, Diagnosis, Surgical Management, and Medical Treatment.

Ten percent of all women have pigmented vulvar lesions. Fortunately, most of these are benign but 1% of all melanomas in women affect the vulva. While the mortality rate of cutaneous melanoma has dropped by 7% annually during the last 5 years, the prognosis of vulvar melanoma remains dismal: the 5-year overall survival rate is 47% compared with 92% for cutaneous melanoma. The current evidence suggests that this likely results from a combination of delayed diagnosis and different tumor biology, treatment strategies, and treatment response. Although many landmark trials on checkpoint inhibitors included mucosal and vulvar melanomas, the results were often not reported separately. Post-hoc analyses indicate overall response rates between 19 and 37% for checkpoint inhibitors. A recently published retrospective study on vulvar melanomas suggests an objective response in 33.3% with a similar safety profile to cutaneous melanoma. Tyrosine kinase inhibitors may be considered in recurrent disease if a c-KIT mutation is present.

Risk of melanoma in women with endometriosis: A Scottish national cohort study

ObjectiveTo explore the risk of melanoma in women with endometriosis. Study DesignA retrospective cohort study using Scottish national population-based data was conducted. The study comprised 281,937 women with nearly 5 million person years (4,923,628) of follow up from 1981 to 2010. 17,834 women with a new surgical diagnosis of endometriosis were compared with 83,303 women with no evidence of endometriosis at laparoscopy, 162,966 women who underwent laparoscopic sterilisation and 17,834 age-matched women from the general population to determine the risk of melanoma. Cox proportional hazards regression was used to calculate crude and adjusted Hazards ratios with 95 % Confidence Intervals. ResultsWomen with endometriosis had a significantly higher risk of melanoma when compared to women with no evidence of endometriosis at laparoscopy (HR 1.59, 95 % CI 1.19–2.13), women who had undergone laparoscopic sterilisation (HR 1.82, 95 % CI 1.39–2.40) and age-matched women from the general population (HR 1.63, 95 % CI 1.08–2.45). ConclusionA diagnosis of endometriosis was associated with an increased risk of developing melanoma compared to those without endometriosis. These findings highlight the need for further research to explore shared pathways in the pathogenesis of the two conditions. It is important to acknowledge that the absolute increase in the risk of melanoma in women with endometriosis remains low, which should be considered when counselling women.

Effects of Exogenous Hormones and Reproductive Factors on Female Melanoma: A Meta-Analysis.

Epidemiological findings on the effects of hormones on melanoma risk have been inconsistent. We therefore conducted a meta-analysis to examine the relationship between exogenous hormonal and reproductive factors and the risk of melanoma in women. We performed a search of PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) database through April 2020 for relevant studies. Based on heterogeneity, we performed the meta-analysis of the risk estimates using either fixed effect or random effect models. We identified 38 studies that met the analytical criteria, involving 3,571,910 participants. The results showed that long-term use of oral contraceptives (OC) may increase the risk of melanoma in women (≥5 years [pooled RR=1.18; 95% CI: 1.07–1.31; I2=0%] and ≥10 years [pooled RR=1.25; 95% CI: 1.06–1.48; I2=0%]). Women who first used OC 15–19 years previously were more likely to develop melanoma (pooled RR=1.52; 95% CI: 1.03–2.24; I2=0%), while the years since the last use and the age at first use were not associated with the development of melanoma in women. Hormone replacement therapy (HRT) increased the incidence of melanoma in women (pooled RR=1.12, 95% CI: 1.02–1.24; I2=50%) and was especially associated with an increased risk of superficial spreading melanoma (SSM) (pooled RR=1.26; 95% CI: 1.17–1.37; I2=0%), and estrogen and estradiol may be the main active agents that contribute to the increased risk of melanoma, but these results may be due to a combination of sun exposure factors. With regard to reproductive factors, decreased parity and being aged ≥20 years at first birth may be associated with an increased risk of melanoma in females, while menopausal status and age at menarche are not associated with the incidence of melanoma in females. Further large-scale prospective studies are necessary to reveal new pathophysiological mechanisms and new therapeutic targets for cutaneous melanoma.

Abstract PR16: Specific activation of the G protein-coupled estrogen receptor inhibits melanoma and other cancers and potentiates immune and targeted therapies

Abstract Modern immune and targeted therapies appear more effective against advanced melanoma in women than in men. Melanoma incidence is also lower in women. Similar sex differences are observed in other tumors that are not classically considered sex hormone responsive. Here, we show that much of the protective effect likely results from estrogen signaling through the G protein-coupled estrogen receptor (GPER) on tumor cells. Selective GPER activation in primary male and female melanocytes, and in melanoma cells, induced long-term changes that maintained a more differentiated cell state as defined by increased expression of well-established melanocyte differentiation antigens, increased pigment production, decreased proliferative capacity, and decreased expression of the oncodriver and stem cell marker c-Myc. GPER signaling also rendered melanoma cells more vulnerable to immunotherapy. Systemic delivery of a small-molecule, selective GPER agonist was well tolerated, and cooperated with PD-1 directed immune checkpoint blockade in melanoma-bearing mice to dramatically extend survival, with up to half of mice clearing their tumor. Complete responses were associated with immune memory that protected against rechallenge with naive tumor cells. Specific GPER activation in the BRaf-driven murine melanoma model (YUMM1.7) also delayed resistance to targeted BRaf inhibition in vivo. Similar antitumor responses were observed in genetically defined KRas-driven syngeneic pancreatic ductal carcinoma (PDAC) models. The GPER agonist used has favorable pharmacokinetics and oral bioavailability in mice and higher vertebrates and appears to have a large therapeutic window. Together, these data suggest that GPER may be a useful, pharmacologically accessible target for melanoma and other common cancers. This abstract is also being presented as Poster B15. Citation Format: Chris Natale, Jinyang Li, Jun Zhang, Cristina Aquirre, Ankit Dahal, Tzvete Dentchev, John Seykora, Ben Stanger, Todd Ridky. Specific activation of the G protein-coupled estrogen receptor inhibits melanoma and other cancers and potentiates immune and targeted therapies [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr PR16.

Cancer cure for 32 cancer types: results from the EUROCARE-5 study.

Few studies have estimated the probability of being cured for cancer patients. This study aims to estimate population-based indicators of cancer cure in Europe by type, sex, age and period. 7.2 million cancer patients (42 population-based cancer registries in 17 European countries) diagnosed at ages 15-74 years in 1990-2007 with follow-up to 2008 were selected from the EUROCARE-5 dataset. Mixture-cure models were used to estimate: (i) life expectancy of fatal cases (LEF); (ii) cure fraction (CF) as proportion of patients with same death rates as the general population; (iii) time to cure (TTC) as time to reach 5-year conditional relative survival (CRS) >95%. LEF ranged from 10 years for chronic lymphocytic leukaemia patients to <6 months for those with liver, pancreas, brain, gallbladder and lung cancers. It was 7.7 years for patients with prostate cancer at age 65-74 years and >5 years for women with breast cancer. The CF was 94% for testis, 87% for thyroid cancer in women and 70% in men, 86% for skin melanoma in women and 76% in men, 66% for breast, 63% for prostate and <10% for liver, lung and pancreatic cancers. TTC was <5 years for testis and thyroid cancer patients diagnosed below age 55 years, and <10 years for stomach, colorectal, corpus uteri and melanoma patients of all ages. For breast and prostate cancers, a small excess (CRS < 95%) remained for at least 15 years. Estimates from this analysis should help to reduce unneeded medicalization and costs. They represent an opportunity to improve patients' quality of life.

Association between menopausal hormone therapy and melanoma: a systematic review and meta-analysis

Abstract Background Age-specific incidence rates of cutaneous Malignant Melanoma (MM) are higher in women during their reproductive years, while the rate of increase slows after menopause, supporting the speculation that hormones might influence the risk of developing cutaneous MM. The aim of our systematic review and meta-analysis is to summarize the evidence on the association between Menopausal Hormone Therapy (MHT) and the risk of MM. Methods Medline and Web of Science were systematically searched for eligible publications until December 2019. Our review and meta-analysis follow the PRISMA guidelines. Heterogeneity testing was performed using Cochran's Q and I2 statistics. Publication bias was assessed by Egger's test and Begg's test. Meta-analysis was performed using a random effect model. Results The pooled analysis of all 19 studies (9 cohort and 10 case-control) showed a significant positive association of MHT with risk of MM (OR 1.19; 95% CI 1.13-1.26; I2=41.93%, p = 0.029). Excluding Uveal and intraocular MM (3 studies), MHT increased the risk of cutaneous MM (OR 1.19; 95% CI 1.13-1.26; I2=35.73%, p = 0.077). No significant publication bias could be detected. Stratifying by study design, MHT significantly increased the risk of cutaneous MM (OR 1.19; 95% CI 1.12-1.27; I2=42.52%, p = 0.107) in the cohort studies; no significant association was found in case-control studies. Conclusions This meta-analysis of available literature resulted in an increased risk of MM in women used MHT. Further investigations are necessary to increase the reliability of the results and estimate the relationship of other characteristics of MHT, such as type (opposed and unopposed estrogens) and route of administration, with MM. Key messages Menopausal Hormone Therapy (MHT) significantly increases the risk of Malignant Melanoma (MM). Further awareness of clinical practitioners should be raised on the potential association of MHT with MM.

When is a cancer patient cured? (Results from the EUROCARE-5 study)

Abstract Background Although heterogenous risks of recurrence or late effects according to cancer type and host factors exist, increasing evidence of cure has emerged for some cancers. This leads, among other important topics, to the so-called “right to be forgotten” law, adopted in France and Belgium to help cancer survivors access loans and insurance. The aim of the study was to estimate population-based indicators of cancer cure in Europe by type, sex, age, and period. Methods Data from 7.2 million cancer patients, aged 15-74 years, from 42 population-based cancer registries in 17 countries were extracted from the EUROCARE-5 dataset. Mixture-cure models were used to estimate: a) median life expectancy of fatal cases (LEF); b) cure fraction (CF) as a proportion of patients with death rates similar to the general population; and c) time to cure (TTC) as the time to reach five-year conditional relative survival (CRS)&amp;gt;95%. Results LEF ranged from 10 years for patients with chronic lymphocytic leukemia to &amp;lt; 6 months for those with liver, pancreas, brain, gallbladder, and lung cancers. The CF was 94% for testis, 87% for thyroid cancer in women (70% in men), 86% for skin melanoma in women (76% in men), 66% for breast, 63% for prostate, and &amp;lt;10% for liver, lung, and pancreatic cancers. TTC was &amp;lt;5 years for testis and thyroid cancer patients diagnosed below age 55 years, and &amp;lt;10 years for stomach, colorectal, corpus uteri, and melanoma patients of all ages. For breast and prostate cancers, a small excess remained for at least 15 years. Conclusions In a context of increasing number of people living after a cancer diagnosis, these results may help to reduce unneeded medicalization (e.g., follow-up) and resources needed for their care, and they further document that there is already a cure for some cancers. Fundings This work was supported by the Italian Association of Cancer Research (AIRC) and the European Commission (IPAAC). Key messages Cancer cure indicators are provided for European patients and 32 cancer type. Recognizing cancer patients as cured has relevant clinical and social implications.

Long Term Survivor of Vaginal Primary Malignant Melanoma

Primary malignant melanoma of the vagina is a rare entity which constitutes less than 3% of vaginal cancer and only 0.3-0.8% of all melanomas in women. It has a high risk of local recurrence and distant metastasis. Once a recurrence is noted, survival is extremely poor. This article reports a case of primary vaginal melanoma with longer survival. As long-time survival of stage II vaginal melanoma is a rare phenomenon, this case is a unique one in Bangladesh; emphasizing on both importance of routine gynaecological examination for any suspicious pigmented lesions in the vagina as well as the necessity of further research on validating treatment protocols.&#x0D; Journal of Armed Forces Medical College Bangladesh Vol.15 (1) 2019: 114-115

Trends in cancer incidence and survival in the Augsburg study region—results from the Augsburg cancer registry

ObjectivesKnowledge about time trends of cancer incidence and cancer survival in a defined region is an essential prerequisite for the planning of regional healthcare infrastructure. The aim of the study...

Vitamin D, melanoma risk, and tumor thickness in PLCO cancer screening trial patients.

The incidence of melanoma is increasing. Other than limiting UV exposure, few factors prevent or reduce the risk of melanoma. The aim of this study is to evaluate the relationship between vitamin D intake and melanoma risk in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. A secondary data analysis was performed on PLCO data. More than 1,300 participants developed melanoma. Melanoma risk may be increased among men within the highest quartile of vitamin D intake (HR 1.27, 95% CI 0.99, 1.61). Women in the highest quartile of vitamin D intake had a decreased risk of invasive melanoma (HR 0.63, 95% CI 0.41, 0.96). Higher education and being white corresponded with deeper tumors (P < .001). High reported vitamin D intake resulted in an increased risk of melanoma among men. Vitamin D intake yielded a protective effect against invasive melanoma in women.

Cutaneous melanoma in women: Demographic differences in genders, prognostic factors, and survival outcomes

Cutaneous melanoma in women: Demographic differences in genders, prognostic factors, and survival outcomes