South Swedish Health Care Region Research Articles

Psychological Resilience and Health-Related Quality of Life in Swedish Women with Newly Diagnosed Breast Cancer.

PurposePsychological resilience appears to be an important influencing factor in various aspects of health-related quality of life (HRQoL) in a context of adversity, eg, being informed of a cancer diagnosis. The purpose was to investigate psychological resilience and HRQoL in Swedish women with newly diagnosed breast cancer in relation to demographic and clinicopathological characteristics.MethodsA population-based cross-sectional study was conducted including 517 women with breast cancer in the South Swedish Health Care Region. Participants were enrolled at the time of consultation for the diagnosis. Psychological resilience was assessed with the Connor-Davidson Resilience Scale 25 (CD-RISC25), and HRQoL was assessed with the Short Form Health Survey. The participants responded to questions regarding demographic variables. Clinicopathological data were collected from the Swedish National Quality Register for Breast Cancer.ResultsThe mean score for psychological resilience was 70.6, identifying 15% of included patients with a score lower than 58 (−1 standard deviation). The study cohort had significantly lower mean scores for several aspects of HRQoL compared with Swedish normative data. Regression analyses demonstrated that psychological resilience was significantly associated with all domains of HRQoL after adjustment for demographic and clinicopathological factors.ConclusionHigher levels of psychological resilience were significantly related to higher levels of HRQoL in Swedish women with newly diagnosed breast cancer and no modifying factor was identified. The assessment of psychological resilience at the time of breast cancer diagnosis might allow for early identification of women in need of more intense psychosocial support. Future studies are needed to identify a clinically relevant threshold of the CD-RISC25.

Variations in the Referral Pattern for Genetic Counseling of Patients with Early-Onset Breast Cancer: A Population-Based Study in Southern Sweden

Swedish national breast cancer guidelines recommend that all women diagnosed with breast cancer (BC) at the age of 35 years or younger should be referred to their regional oncogenetic clinic for genetic counseling and testing, regardless of family history of cancer. The main objective of this study was to evaluate whether place of residence at BC diagnosis and treating hospital were associated with the fact that not all BC patients diagnosed at ≤35 years in the southern part of Sweden have attended genetic counseling and testing. Between 2000 and 2013, 279 women in the South Swedish Health Care Region were diagnosed with BC at ≤35 years. Information regarding place of residence at BC diagnosis, treating hospital, time of registration and first meeting at the Oncogenetic Clinic in Lund, and genetic testing was collected. With a follow-up period until August 2018, 64% were registered at the clinic (60% underwent genetic testing) and 36% were not. BC patients from 2 counties and from rural settings with a population of <10,000 inhabitants were significantly less likely to be registered at the clinic. Our results suggest that place of residence at BC diagnosis and treating hospital were associated with the probability of referral for genetic counseling and testing for women diagnosed with BC at ≤35 years in the South Swedish Health Care Region. We propose, as a generalizable finding, that further educational and outreach activities within the health care system and the community may be needed to ensure that all women diagnosed with early-onset BC receive proper genetic counseling.

Identification of Warning Signs During Selection of Surgical Trainees

The aim was to document empirical observations about antecedents to and practices of unsuitable behaviours amongst surgical trainees and develop an interview guide that could be used for the selection process. A mixed methods design was adopted combining a survey distributed to senior surgeons and heads of departments, followed by semi-structured interviews with experienced surgeons. All surgical departments and hospitals in The South Swedish Health Care Region. The survey was completed by 54 of 83 eligible surgeons above 50years of age, and 4 of 7 heads of surgical departments. Semi-structured interviews with 13 surgeons representing local, regional, and university hospitals from the same cohort. Forty-six (85%) surgeons and four of seven heads of departments responded that they had come across surgical trainees deemed unsuitable to train and work as a surgeon. All heads of department and 31 of 54 of the surgeons believed tendencies towards unsuitability are evident early during training. From the survey, 107 statements described reasons for finding a trainee unsuitable. Qualitative analysis of the interviews and free-text answers of the survey led to identification of 11 problem domains with associated "warning signs". An interview guide to help detect unsuitability tendencies in candidates during selection procedures was constructed. Experienced surgeons have quite consistent views on what makes a person unsuitable as a surgeon. Their views have been systematized into 11 problem domains, and a set of 'warning signs' for unsuitable behaviours and traits has been developed. Early detection of these signs and traits is important for the individual, the work environment, and patient safety. A recommendation for a minimum framework for selection including the constructed interview guide is presented.

Abstract P1-06-01: Putting multigene signatures to the test: Prognostic assessment in population-based contemporary clinical breast cancer

Abstract Background Gene expression signatures hold promise for a molecularly driven division of primary breast cancer with clinical implications. A gap still remains in the application/validation of such signatures in actual clinical treatment groups from unselected, population-based, primary breast cancer receiving current standard of care therapy. We analyzed classification proportions and overall survival (OS) of 14 reported gene expression phenotypes (GEPs) and risk predictors (RPs) in seven clinical treatments groups from an 3273-sample breast cancer cohort representative of population-based disease in the South Swedish healthcare region. Patients and methods Between 2010-09-01 to 2015-03-31, 5101 (87%) of 5892 patients with invasive primary disease in the healthcare region were included in the SCAN-B study (ClinicalTrials.gov ID: NCT02306096). Inclusion criteria included no generalized/prior contralateral disease and known surgery/treatment status (neo- or adjuvant). 3273 tumors were profiled by RNA sequencing and matched to clinicopathological patient data from the National Breast Cancer Register, with distribution of clinicopathological characteristics reflecting proportions in the catchment region. RNA profiles were classified according to 14 reported gene signatures featuring both GEPs (PAM50, IC10, CIT, TNBCtype) and specific risk predictors (e.g. Oncotype Dx, 70-gene, 76-gene, ROR-variants, genomic grade index). Classifications were investigated for association with patient OS by univariate and multivariate analyses in seven adjuvant clinical treatment groups: TNBC-ACT (adjuvant chemotherapy, n=228), TNBC-untreated (n=83), HER2+/ER- with trastuzumab + ACT treatment (n=101), HER2+/ER+ with trastuzumab + ACT + endocrine treatment (n=210), ER+/HER2- with endocrine treatment (n=1477), ER+/HER2- with endocrine + ACT treatment (n=637), and ER+/HER2- untreated (n=216). Results For the majority of signatures, analysis of classification demonstrated prognostic value limited to ER+/HER2- tumors given follow-up time. Several signatures (including Oncotype Dx, 70-gene, ROR-variants) showed strong predictive value in identifying a subset of ER+/HER2- patients receiving a combination of endocrine and ACT therapy with excellent overall survival (&amp;gt;96%), indicating appropriate therapy selection. In addition, for both ER+/HER2- treatment groups signature analysis identified high-risk groups of patients in clear need of additional treatment beyond standard therapeutic regimes, even with less than 5-years of follow-up. Conclusions Our results support the prognostic association of gene expression signatures in large unselected population-based primary breast cancer cohorts even with a short follow-up of OS.Importantly, prognostic associations are limited to specific subgroups for different classifiers and in population-based breast cancer some clinically important subgroups constitute a small proportion of cases. In this context, continued population-based inclusion and broad transcriptional profiling of breast cancer patients provides an opportunity for application to broader patient groups (e.g. TNBC and HER2+), and for consensus classification of individual risk assessments that could potentially provide more stable predictions. Citation Format: Staaf J, Vallon-Christersson J, Häkkinen J, Saal LH, Hegardt C, Larsson C, Ehinger A, Ryden L, Loman N, Malmberg M, Borg Å. Putting multigene signatures to the test: Prognostic assessment in population-based contemporary clinical breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-01.

Prevalence of human papillomavirus types, viral load and physical status of HPV16 in head and neck squamous cell carcinoma from the South Swedish Health Care Region.

Incidence of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is rising in several countries. Intriguingly, large variations of HPV16 viral load and different proportions of the physical viral status among HNSCC have been reported. We analysed fresh biopsies of 275 HNSCC patients from the South Swedish Health Care Region for HPV types with modified general primer PCR and Luminex. Seventy-eight HPV16-positive HNSCC cases were further investigated for viral DNA load and physical status using quantitative PCR for HPV E2 and E7 genes. Presence of intact E2 gene, as a surrogate marker for episomal HPV, was investigated with conventional PCR. Fifteen different HPV types were detected in HNSCC cases and HPV16 was present in 74 % of the HPV-positive cases. HPV was detected in 65 % (92/141) and 11 % (15/134) of oropharyngeal and non-oropharyngeal carcinomas, respectively (P<0.0001). HPV was detected in 73 % (75/103) of tonsillar carcinomas. The median load of HPV16 was 13 copies cell-1 (range 0.003-1080). Among HPV16-positive patients with oropharyngeal carcinoma, metastases to regional lymph nodes were observed in 100 % (17/17) and 68 % (40/58) for those with <1 HPV16 copy cell-1 and >1 HPV16 copy cell-1, respectively (P=0.007). Among HPV16 cases, purely integrated HPV16 was found in 6 %, whereas entirely episomal and mixed virus was detected in 51 and 42 % of cases, respectively. Conclusively, HPV16 viral DNA load demonstrated a large diversity among HNSCCs. Although integration of HPV16 is common (48 %), the episomal HPV16 is salient (93 %) among HPV16 HNSCCs. In addition, low amount of HPV16 was associated with lymph node metastases among oropharyngeal carcinomas.

Abstract 2548: Cancer in first-degree relatives of women with early-onset breast cancer: a comparison of self-reported and cancer registry data

Abstract Background Breast cancer (BC) is the most common cancer in women, both world-wide and in Sweden. However, only about 2% occur in women ≤35 years of age. The aim of this study was to compare self-reported and registry data of family history of cancer, tumor characteristics and BRCA germline mutation status in women with early-onset BC. Materials and methods Between January 1st 1990 and December 31st 2013, a total of 779 women aged ≤35 years were diagnosed with BC in the South Swedish Health Care Region. Of these women, 231 women sought, or were referred for, genetic counseling at the Oncogenetic Clinic, Lund, Sweden, and were included in the study. Subsequently, 224 women were screened for germline mutations. Self-reported information about family history of cancer in first-degree relatives (parents, siblings and children) was obtained from the participants and was compared with data from the Swedish Cancer Registry. When available, hormone receptor (ER and PR) and HER2 status of the tumors was collected from pathology reports. Fisher's Exact Test was performed to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results Mutation analyses revealed 143 (63.8%) cases without mutations (BRCAX), 46 (20.5%) with BRCA1, 19 (8.5%) with BRCA2 and 16 (7.1%) with other mutations (TP53, CHEK2, PTEN, PALB2, CDH1 and MSH2/MSH6). Family history of BC and ovarian cancer (OvC) in first-degree relatives was self-reported in equal numbers as registry data. Family history of BC was found in ∼30% of the cases, and of OvC in ∼3%. However, family history of other types of cancer was self-reported in 13 (5.6%) and registry-reported in 58 (25.1%) cases (OR, 18.8; 95% CI, 3.91-180; p&amp;lt;0.001). Of the registry-reported cancers, cervical and skin cancers were the most common when diagnosed before the genetic counseling sessions, and when diagnosed after, prostate and skin cancers were the most common. When comparing tumor characteristics of BRCA1 with BRCAX cases, mutation carriers more often showed receptor negative tumors: ER- (OR, 13.4; 95% CI, 3.77-73.5; p&amp;lt;0.001), PR- (OR, 47.9; 95% CI, 7.34-2011; p&amp;lt;0.001) and HER2- (OR, 17.1; 95% CI, 1.81-inf; p&amp;lt;0.004). Conclusion The main findings in this study of early-onset BC were that cases with germline mutations in the BRCA1 and BRCA2 genes were exceptional high, that cervical cancer was the most common not self-reported cancer in first-degree relatives diagnosed before the genetic counseling, and that BRCA1 carriers had a higher rate of ER, PR and HER2 negative tumors, which tends to indicate a less favorable prognosis. When assessing the need for mutation screening, as shown previously by others, oncologists and genetic counselors need to consider both early-onset BCs and receptor negative tumors as predictors for BRCA1 mutations, and when obtaining information about family history of cancers, patients might lack information about cervical cancers in relatives. Citation Format: Annelie Augustinsson, Ulf Kristoffersson, Håkan Olsson. Cancer in first-degree relatives of women with early-onset breast cancer: a comparison of self-reported and cancer registry data. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2548.

Abstract 2747: Increasing age at first full-time pregnancy correlates to use of oral contraceptives before age 20 in women with a family history of breast cancer

Abstract Background Women with a family history of breast cancer (BC) in first-degree female relatives have an increased risk of BC. The aim of this study was to determine the BC risk associated with exposure to endogenous and exogenous hormones in familial BC compared with non-familial BC. Materials and methods A population-based prospective questionnaire-based cohort was initiated in 1990 in the South Swedish Health Care Region. Forty thousand healthy women between ages 25 to 65 years were randomly selected, out of which 29,520 answered the first questionnaire. Data was subsequently collected from several registries and a second questionnaire. Familial BC was defined as having first-degree relatives (mother, sisters, and/or daughters) diagnosed with BC. Known mutation carriers in BRCA-related genes (n = 13) were excluded from all analyses. To determine whether there are any differences between familial and non-familial BC risk according to hormonal exposures, Cox proportional hazard models were used. Hazard ratios (HR) were estimated with 95% confidence intervals (CI), and all models were adjusted for birthdate. Results At the end of follow-up (10/31/2013), 1,500 (5%) of the women were diagnosed with BC. Out of the 1,500 BC cases, 192 women (13%) had a family history of BC. Having a family history of BC in first-degree relatives was twice as prevalent among BC cases compared with women without BC diagnosis (OR 1.9 (CI 1.63-2.23)). When adjusting for age at menarche and ever-use of oral contraceptives (OC), an increased age at first full-time pregnancy was associated with an increased risk of BC, both for BC cases with familial BC and non-familial BC, HR 1.02 (CI 1.00-1.03) and HR 1.01 (CI 1.00-1.02), respectively. Adjusted for age at menarche and parity, an increased risk of BC was associated with use of OC before age 20 (HR 1.7 (CI 0.99-2.80)) for BC cases with familial BC compared with non-BC cases with familial BC. This was not observed in women with non-familial BC. Conclusion The main findings in this study were that older age at first full-time pregnancy has a larger impact on BC risk in women with familial BC than in women without, and that use of OC before age 20 increases the risk of BC in women with familial BC, not observed in women without. Well known familial and/or hormonal risk factors for BC were observed in our study, implying the validity of the cohort. Our results indicate similarities in risk of BC between women with, and without, familial BC regarding age at first full-term pregnancy. However, the impact seems to be larger in familial BC. If confirmed in other studies, our findings could be of interest for women with familial BC, especially regarding the increased risk when using OC during adolescence, where other alternatives are available. Citation Format: Annelie Augustinsson, Carolina Ellberg, Ulf Kristoffersson, Håkan Olsson. Increasing age at first full-time pregnancy correlates to use of oral contraceptives before age 20 in women with a family history of breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2747. doi:10.1158/1538-7445.AM2015-2747

Absence of the common IGF1 19 CA-repeat allele is more common among BRCA1 mutation carriers than among non-carriers from BRCA1 families

BRCA1 mutations predispose to early-onset breast cancer. We previously reported an association between absence of the common IGF1 19 CA-repeat allele (IGF1-19/-19) and being a BRCA1 mutation carrier in young women from breast cancer high-risk families. Others have reported a four-fold risk of premenopausal breast cancer in women with a family history and the IGF1-19/-19 genotype. The aim of this study was to investigate whether the IGF1-19/-19 genotype was associated with being a BRCA1 mutation carrier among women from BRCA1 families. DNA was available from 268 women with known BRCA1 status from the South Swedish Health Care Region. IGF1 genotyping was successfully performed with fragment analysis in 211 women from 96 families. The IGF1-19/-19 genotype was significantly more common among BRCA1 mutation carriers (14.2%) than among non-carriers (4.8%), OR 3.3 (95%CI 1.11-9.78, P = 0.03) adjusted for family clustering. We confirmed our previous finding of an association between the IGF1-19/-19 genotype and BRCA1 mutation status. Since the IGF1-19/-19 genotype in combination with OC use or multiparity confers an increased risk for early onset breast cancer in high-risk women and in women from the general population, future studies are needed to elucidate the importance of the IGF1-19/-19 genotype concerning the variability in breast cancer risk among BRCA1 mutation carriers.

Impact of teenage oral contraceptive use in a population-based series of early-onset breast cancer cases who have undergone BRCA mutation testing

Oral contraceptive (OC) use in young women has been associated with an increased risk of breast cancer. This matched case-control study aims to elucidate the combined effects of OC use and genetic factors in a population-based series of BRCA1/2 mutation-tested early-onset breast cancers. A first invasive breast cancer was diagnosed in 259 women aged ⩽40 years between 1990 and 1995 in the South Swedish Health Care Region. A total of 245 women were included in this study. Information on family history of cancer, reproductive factors, smoking and OC use was obtained from questionnaires or patient charts. Three age-matched controls per case were chosen from a prospective South Swedish cohort. Ever OC use and current OC use were not associated with breast cancer. Cases were more likely to have used OCs before age 20 years (adjusted odds ratio (OR) 2.10 (95% CI 1.32–3.33)) and before their first child (adjusted OR 1.63 (95% CI 1.02–2.62)). When stratified by age, the effect of early OC use was limited to women diagnosed prior to age 36 years (OR 1.53 (1.17–1.99) per year of OC use prior to age 20 years). The risks were similar for low-dose and high-dose OCs. The probability of being a BRCA1/2 mutation carrier was three times higher among cases who started OC use prior to age 20 years compared with cases who started at age 20 years or older or who had never used OCs. However, the duration of OC use was similar among cases with and without BRCA1/2 mutations. No association was seen with a first-degree family history of breast cancer. Each year of OC use prior to age 20 years conferred a significantly increased risk for early-onset breast cancer, while there was no risk associated with use after age 20 years.

The need for oncogenetic counsellingTen years’ experience of a regional oncogenetic clinic

A monogenic inheritance, mainly seen as a dominant pattern, accounts for 5–10% of all cancer cases. The increased knowledge and identification of high-risk genes have led to a need for specialized cancer family clinic was the expression used by Eeles and Murday. The Oncogenetic Clinic at the University Hospital in Lund was started in 1993 and the authors’ 10-year experience is summarized in this paper. The clinic offers service to the South Swedish Health Care Region comprising a total of 1.6 million inhabitants. During these first 10 years a total of 1 059 individuals from 789 families have been individually counselled. The most common reason for referral was a family history of breast cancer, followed by a family history of colorectal cancer. According to the commonly used criteria, 437 (55%) of the families were considered as autosomal dominantly inherited; 147 families (19%) did not fulfil these criteria but had a strong clustering of breast/ovarian or colorectal/endometrial cancer. The remaining 205 families (26%) were not recognized as any previously described hereditary cancer syndrome with early onset. However, most of these families had a family history of cancer. Mutation analysis was performed in 386/789 (49%) of the families. In families with breast and ovarian cancer a genetic aberration was identified in 45/76 (59%) and in breast-only families in 27/129 (21%). In MSI-positive colon cancer families 16/34 (47%) of the families had a germline mutation. Thus, the majority of the families referred to the clinic were in obvious need of genetic counselling concerning cancer and heredity and in a substantial number of the families a germline mutation could be identified.

Reproducibility of a self-administered questionnaire for assessment of melanoma risk.

The reproducibility of a self-administered questionnaire on different epidemiological variables was examined in a random sample of a cohort of healthy women from the South Swedish Health Care Region. An identical questionnaire has previously been used for assessment of melanoma risk, in a population-based, matched, case-control study from the same region. Repeat questionnaires were completed on two occasions, 1-3 years apart, by 670 randomly selected subjects. In addition, exposure data from a case-control study were used to estimate the effect of misclassification. Overall, there was a fair to good consistency between the answers on the two occasions for the various epidemiological variables. Exposure variables identified as risk factors for melanoma development were reasonably reproducible. The estimated proportion of agreement, A, ranged from 0.74 to 0.92, the average correct classification rate (assuming common sensitivity and specificity), pi, was > or = 0.85 and the kappa coefficient, kappa, ranged between 0.52 and 0.83. However, the question on number of raised naevi on the arm was an exception since it had a lower test-retest reliability (A = 0.62, pi = 0.77, kappa = 0.40). When using data from the case-control study, the effect of the estimated random misclassification was found to only slightly bias odds ratios toward one. Our questionnaire, used for assessment for melanoma risk, provided information with fair to good test-retest reliability, and corrected odds ratios were found to be only slightly higher than observed odds ratios.

Is the use of sunscreens a risk factor for malignant melanoma?

The relation between use of sunscreens, different host factors and malignant melanoma was investigated in a population-based, matched case-control study of malignant melanoma in the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, between 1 July 1988 and 30 June 1990. In total, 400 melanoma patients and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire regarding different epidemiologic variables, including questions on use of sunscreens and different constitutional factors. The use of sunscreens was not found to protect against developing malignant melanoma. Instead, an unexpected relation between the use of sunscreens and the risk of developing malignant melanoma was seen (odds ratio (OR) 1.8 for almost always vs never using sunscreens). A tentative dose-response relation was found. Virtually the same ORs were seen in both sexes. Furthermore, persons younger than 50 years had a higher OR than persons older than 50 years. When different melanoma presentation sites were considered, lesions of the trunk were associated with sunscreen use in females (adjusted OR = 3.7 for almost always vs never using sunscreens), while lesions of the extremity or head and neck were associated with sunscreen use in males (adjusted OR = 3.2 for almost always vs never using sunscreens). Raised naevi on the left arm and freckling were shown to be the major constitutional risk factors (OR = 3.9 for more than three naevi vs none and OR = 1.4, respectively). The results were essentially unaltered in a histopathologically re-examined material. Further investigations are needed in order to form a basis for melanoma prevention.

Use of Sunbeds or Sunlamps and Malignant Melanoma in Southern Sweden

In a population-based, matched case-control study from the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, the relation between the use of sunbeds or sunlamps and malignant melanoma was investigated. Between July 1, 1988, and June 30, 1990, a total of 400 melanoma patients and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire containing different epidemiologic variables. Questions regarding the use of sunbeds or sunlamps were included. The odds ratio for developing malignant melanoma after ever having used sunbeds or sunlamps was 1.3. Considering all age groups, the odds ratio was significantly elevated after exposure more than 10 times a year to sunbeds or sunlamps (odds ratio (OR) = 1.8). When the study was restricted to patients and controls younger than age 30 years because the use of tanning devices is much more common among young persons, the odds ratio was higher (OR = 7.7 for more than 10 times a year vs. none). These findings were independent of constitutional factors and factors regarding sun exposure. A dose-response relation was evident. Furthermore, among melanoma patients in this young age group, the ratio of females to males was significantly higher than in older patients. When different melanoma presentation sites were considered, only lesions of the trunk were significantly associated with sunbed or sunlamp use (OR = 4.2 for more than 10 times a year vs. none).

Cutaneous malignant melanoma in South Sweden 1965, 1975, and 1985. A histopathologic review

There is an increase in the incidence of cutaneous malignant melanoma (CMM) among white people throughout the world. In Sweden, a fivefold increase has been recorded since 1960, but the mortality is rising at a much lower rate. Tumor thickness is the single most important prognostic factor for primary melanoma. This study aimed to clarify whether the thickness of the tumor in invasive CMM decreased during the period 1965-1985. This population-based study identified 574 cases of CMM, both invasive and noninvasive, in the South Swedish Health Care Region in 1965, 1975, and 1985. Twenty-six cases were excluded because the collection or evaluation of the material was not possible. The remaining 548 cases were reviewed histopathologically, and a diagnosis of invasive CMM was rejected in 71 cases. Eventually, 467 cases of invasive melanoma remained in our study (70 in 1965, 124 in 1975, and 273 in 1985). The level of invasion, tumor thickness, regression, ulceration, presence of inflammatory cells, benign naevus cells, and the site of presentation were studied. The study found neither a significant decrease of tumor thickness of invasive CMM nor changes in the level of invasion or proportion of ulcerated melanoma. A significantly higher proportion of melanoma tumors containing benign naevus cells was seen throughout the years (P < 0.05). Women had significantly fewer inflammatory cells in their tumors than did men (P < 0.01). As expected, the anatomical site of presentation showed a significant sex-related difference, with more tumors on the legs of female patients and more on the trunk of male patients (P < 0.001). There is a divergence between the rapidly increasing incidence and the slower increase in mortality of CMM. This cannot be explained by a removal of the melanoma at a thinner thickness. Differences between the sexes according to the tumor site and the increasing rate of CMM containing benign naevus cells could implicate changes in the tumor biology. Public education in Sweden concerning ultraviolet radiation and the connection with melanoma is fairly new and might not have any influence on this time period. Additional investigation is needed to clarify this matter.

At what age do sunburn episodes play a crucial role for the development of malignant melanoma

The age relationship between sunburns and malignant melanoma was investigated in a population-based, matched, case-control study from the South Swedish Health Care Region (the highest risk area for melanoma in Sweden). Between 1988 and 1990, a total of 400 patients with a first diagnosis of malignant melanoma and 640 healthy controls aged 15–75 years answered a comprehensive questionnaire including questions regarding ultraviolet radiation exposure. In addition, a literature review was performed. The average number of episodes of sunburn per year was significantly associated with malignant melanoma (relative risk, RR = 1.9 for ≥ three episodes per year versus never). Outdoor employment during the summer was associated with a decreased risk for the development of malignant melanoma (RR = 0.8). Data from case-control studies and migration studies concerning age relationship between sunburns and melanom are inconsistent. From our own data, we did not find a higher risk of melanoma developed in individuals who had experienced severe sunburns in childhood. Instead, a significantly increased risk was associated with sunburns after age 19 years, RR = 2.2 for a history of more than five times versus never. Even if the hypothesis is biologically plausible, that episodes of sunburn early in life are associated with a higher risk of melanoma, so far epidemiological evidence is scarce. There is a need for better prospective epidemiological studies addressing this issue.