Burden of late effects in a nationwide sample of long-term breast cancer survivors.

BACKGROUND: Long-term breast cancer survivors (BCSs) may experience several late effects (LEs) simultaneously. This study aimed to identify subgroups of 8-year BCSs with higher burden of LEs who could benefit from closer survivorship care, explore variables associated with higher symptom burden, and describe how symptom burden may affect general functioning. METHODS: All Norwegian women aged 20 to 65 years when diagnosed with stage I-III breast cancer in 2011 and 2012 were invited (n = 2803). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire/BR23, the Fatigue Questionnaire, Assessment of Survivor Concerns, and Scale for Chemotherapy Induced Long-term Neurotoxicity were used to assess 10 common LEs and general functioning. Using latent class analysis, subgroups of BCSs with similar burden of LEs were identified. Multinominal regression analysis were performed to examine variables associated with higher symptom burden. RESULTS: The final sample consisted of 1353 BCSs; 46% had low, 37% medium, and 17% high symptom burden. Younger age, short education, axillary dissection, higher systemic treatment burden, higher body mass index, and physical inactivity were associated with higher symptom burden. General functioning scores were lower, and the proportion on disability pension were higher among BCSs in the two most burdened subgroups compared with those in the low burden subgroup. CONCLUSION: More than half of long-term BCSs suffered from medium or high symptom burden and experienced impaired general functioning compared with BCS with low symptom burden. Younger age and systemic treatment were important risk factors for higher symptom burden. BCSs at risk of higher symptom burdens should be identified and offered closer and extended survivorship care.

High neuroticism is associated with common late adverse effects in a nationwide sample of long-term breast cancer survivors.

PURPOSE: Neuroticism is a basic personality trait characterized by negative emotions triggered by stress such as a breast cancer diagnosis and its treatment. Due to lack of relevant research, the purpose of this study was to examine if high neuroticism is associated with seven common late adverse effects (LAEs) in long-term (≥ 5 years) breast cancer survivors (BCSs). METHODS: All female Norwegian BCSs aged 20-65 years when diagnosed with stage I-III breast cancer in 2011 or 2012 were invited to a questionnaire study in 2019 (N = 2803), of whom 48% participated (N = 1355). Neuroticism was self-rated using the abridged version of the Eysenck Personality Questionnaire, and scores dichotomized into high and low neuroticism. LAEs were defined by categorization of ratings on the EORTC QLQ-C30 (cognitive function, pain, and sleep problems) and QLQ-BR23 (arm problems) questionnaires, and categorizations of scale scores on mental distress, fatigue, and neuropathy. Associations between high neuroticism and LAEs were explored using multivariate logistic regression analyses. RESULTS: High neuroticism was found in 40% (95%CI 37-42%) of BCSs. All LAEs were significantly more common among BCSs with high compared to low neuroticism. In multivariable analyses, high neuroticism was positively associated with all LAEs except neuropathy. Systemic treatment, somatic comorbidity, and not being in paid work were also significantly associated with all LAEs. CONCLUSIONS: High neuroticism is prevalent and associated with increased risks of LAEs among BCSs. Identification of high neuroticism could improve the follow-up care of BCSs as effective interventions for the condition exist.

Sexual health in long-term breast cancer survivors: a comparison with female population controls from the HUNT study.

PURPOSE: Sexual health is an important aspect of quality of life. Knowledge concerning sexual health in long-term breast cancer survivors (BCSs) is limited. This study compared sexual health in BCSs 8 years after diagnosis with similarly aged controls and examined the impact of menopausal status at diagnosis and systemic breast cancer treatments on sexual health. METHODS: Women aged 20-65 years when diagnosed with stage I-III breast cancer in 2011-2012 were identified by the Cancer Registry of Norway (n = 2803) and invited to participate in a nationwide survey. Controls were women from the Trøndelag Health Study (HUNT4). Sexual functioning and sexual enjoyment were measured by the EORTC QLQ-BR23 subscales scored from 0 to 100, and sexual discomfort by the Sexual Activity Questionnaire scored from 0 to 6. Linear regression analyses with adjustments for sociodemographic and health-related variables were performed to compare groups. Differences of ≥ 10% of range score were considered clinically significant. RESULTS: The study samples consisted of 1241 BCSs and 17,751 controls. Sexual enjoyment was poorer (B - 13.1, 95%CI - 15.0, - 11.2) and discomfort higher (B 0.9, 95%CI 0.8, 1.0) among BCSs compared to controls, and larger differences were evident between premenopausal BCSs and controls (B - 17.3, 95%CI - 19.6, - 14.9 and B 1.2, 95%CI 1.0, 1.3, respectively). BCSs treated with both endocrine- and chemotherapy had lower sexual functioning (B - 11.9, 95%CI - 13.8, - 10.1), poorer sexual enjoyment (B - 18.1, 95%CI - 20.7, - 15.5), and more sexual discomfort (B 1.4, 95% 1.3, 1.6) than controls. CONCLUSION: Sexual health impairments are more common in BCSs 8 years after diagnosis compared to similar aged population controls. During follow-up, attention to such impairments, especially among women diagnosed at premenopausal age and treated with heavy systemic treatment, is warranted.

Late effects after breast cancer treatment. / Seneffekter etter behandling av brystkreft.

Breast cancer is the most common cancer among women in Norway. Nine out of ten will become long-term survivors. Being cancer-free does not necessarily mean feeling healthy, and many experience troublesome late effects, such as fatigue, pain and fear of recurrence. General practitioners represent the most important medical support for the majority of these women. This clinical review article summarises up-to-date knowledge about late effects after breast cancer treatment. Non-pharmacological interventions can have a positive effect on many of the most common late effects.

Sexual activity and functioning in long-term breast cancer survivors; exploring associated factors in a nationwide survey.

PURPOSE: Sexual health is a key quality of life issue. Knowledge concerning sexual health in long-term breast cancer survivors (BCSs) is limited. Within a nationwide sample, we aimed to assess the prevalence of sexual inactivity and to explore factors associated with sexual inactivity and reduced sexual functioning among long-term BCSs. METHODS: Long-term BCSs aged 20-65 years when diagnosed with early-stage breast cancer in 2011-2012 were identified by the Cancer Registry of Norway in 2019 (n = 2803) and invited to participate in a nationwide survey. Sexual health was measured using the multidimensional Sexual Activity Questionnaire. Factors associated with sexual inactivity and reduced sexual functioning were explored using multivariable logistic- and linear regression analyses with adjustments for relevant sociodemographic, health-, and cancer-related variables. RESULTS: The final sample consisted of 1307 BCSs with a mean age of 52 years at diagnosis. Fifty-two percent of the BCSs were sexually inactive. Lack of interest was the most common reason for sexual inactivity. Treatment with aromatase inhibitor (OR 1.73, 95% CI 1.23, 2.43) and poor body image (OR 0.99, 95% CI 0.99, 0.995) were associated with sexual inactivity. Among sexually active BCSs, depression (B - 1.04, 95% CI - 2.10, - 0.02) and physical inactivity (B - 0.61, 95% CI - 1.21, - 0.02) were inversely related to sexual pleasure. Treatment with aromatase inhibitor (B 0.61, 95% CI 0.20, 1.01), sleep problems (B 0.37, 95% CI 0.04, 0.70), breast symptoms (B 0.01, 95% CI 0.003, 0.02), and chronic fatigue (B 0.43, 95% CI 0.05, 0.81) were associated with sexual discomfort. Chemotherapy (OR 1.91, 95% CI 1.23, 2.97), current endocrine treatment (OR 1.98, 95% CI 1.21, 3.25), and poor body image (OR 0.98, 95% CI 0.98, 0.99) were associated with less sexual activity at present compared to before breast cancer. CONCLUSION: Treatment with aromatase inhibitor seems to affect sexual health even beyond discontinuation. Several common late effects were associated with sexual inactivity and reduced sexual functioning. To identify BCSs at risk of sexual dysfunction, special attention should be paid to patients treated with aromatase inhibitor or suffering from these late effects.

Health literacy among long-term survivors of breast cancer; exploring associated factors in a nationwide sample.

BACKGROUND: Poor health literacy may hamper health management and long-term outcomes in breast cancer survivorship. Knowledge of factors associated with poor health literacy is needed to identify survivors in need of additional support and to improve the quality of health care, but is currently scant. Here, we explore health literacy and associated factors in a nationwide sample of long-term survivors of breast cancer. MATERIAL AND METHODS: All survivors aged 20-65 years when diagnosed with stage I-III breast cancer in 2011 or 2012 were identified through the Norwegian Cancer Registry, and invited to participate in the Survivorship, Work and Sexual Health (SWEET) study. Health literacy was measured using The European Health Literacy Survey Questionnaire-12 (HLS-EU-Q12) and analyzed as a continuous and categorical variable. Associations between health literacy and socioeconomic, physical, and mental health variables, including the most common late effects after cancer treatment, were explored in uni- and multivariable linear regression models. RESULTS: The final sample consisted of 1355 survivors (48%) with a mean age of 60 years at survey (SD 8.7). Eight years had passed since diagnosis (SD.0.7), and the majority of survivors had high socioeconomic status. Advanced judgment calls concerning treatment and health risks were reported to be the most difficult for survivors to handle. Mean health literacy sum score was 36.2 (range 12-48, SD 5.4). Thirty-nine percent had intermediate, while 19.3% reported marginal or inadequate health literacy. Education, income, age at diagnosis, the personality trait neuroticism, and fear of cancer recurrence were significantly associated with health literacy in the multivariate model, explaining 12% of the variance in health literacy scores. CONCLUSION: Low levels of health literacy were prevalent in this population-based sample of long-term survivors of breast cancer, despite high socioeconomic status. Communicating and interpreting risks seem to be especially challenging. Attention to health literacy at a societal and individual level is necessary in order to provide survivorship care of high quality.

Hyperemesis gravidarum and maternal cancer risk, a Scandinavian nested case-control study.

Reproductive factors have been shown to influence cancer risk. Several pathological conditions during pregnancy have also been associated with subsequent altered cancer risk in the mother. Hyperemesis gravidarum (hyperemesis) is an early pregnancy condition characterized by severe nausea and vomiting resulting in weight loss and metabolic disturbances. Studies have reported associations between hyperemesis and cancer, but results are inconsistent. In this nested case-control study we linked the population-based medical birth registries and cancer registries in Norway, Sweden and Denmark in order to examine overall cancer risk and risk of specific cancer types in women with a history of hyperemesis, using conditional logistic regression. In total, 168,501 cases of cancer in addition to up to 10 cancer-free controls per case were randomly sampled, matched on year of birth and birth registry (n = 1,721,626). Hyperemesis was defined through the International Classification of Diseases. Analyses were adjusted for potential confounders. Hyperemesis was inversely associated with overall cancer risk with adjusted relative risk (aRR) of 0.93 (95% CI: 0.88-0.99), with cancer in the lungs (aRR: 0.60, 95% CI: 0.44-0.81), cervix (aRR: 0.66, 95% CI: 0.49-0.91) and rectum (aRR: 0.48, 95% CI: 0.29-0.78). Thyroid cancer was positively associated with hyperemesis (aRR 1.45, 95% CI: 1.06-1.99) and risk increased with more than one hyperemetic pregnancy (aRR 1.80, 95% CI: 1.23-2.63). Hormonal factors, in particular human chorionic gonadotropin, are likely to be involved in mediating these effects. This study is the first to systematically address these associations and provides valuable knowledge on potential long-term consequences of hyperemesis.

Hyperemesis gravidarum and risk of cancer in offspring, a Scandinavian registry-based nested case-control study.

BACKGROUND: Hyperemesis gravidarum is a serious condition affecting 0.8-2.3% of pregnant women and can be regarded as a restricted period of famine. Research concerning potential long-term consequences of the condition for the offspring, is limited, but lack of nutrition in-utero has been associated with chronic disease in adulthood, including some cancers. There is growing evidence that several forms of cancer may originate during fetal life. We conducted a large study linking the high-quality population-based medical birth- and cancer registries in Norway, Sweden and Denmark, to explore whether hyperemesis is associated with increased cancer risk in offspring. METHODS: A registry-based nested case-control study. Twelve types of childhood cancer were selected; leukemia, lymphoma, cancer of the central nervous system, testis, bone, ovary, breast, adrenal and thyroid gland, nephroblastoma, hepatoblastoma and retinoblastoma. Conditional logistic regression models were applied to study associations between hyperemesis and risk of childhood cancer, both all types combined and separately. Cancer types with five or more exposed cases were stratified by age at diagnosis. All analysis were adjusted for maternal age, ethnicity and smoking, in addition to the offspring's Apgar score, placental weight and birth weight. Relative risks with 95% confidence intervals were calculated. RESULTS: In total 14,805 cases and approximately ten controls matched on time, country of birth, sex and year of birth per case (147,709) were identified. None of the cancer types, analyzed combined or separately, revealed significant association with hyperemesis. When stratified according to age at diagnosis, we observed a RR 2.13 for lymphoma among adolescents aged 11-20 years ((95% CI 1.14-3.99), after adjustment for maternal ethnicity and maternal age, RR 2.08 (95% CI 1.11-3.90)). The finding was not apparent when a stricter level of statistical significance was applied. CONCLUSIONS: The main finding of this paper is that hyperemesis does not seem to increase cancer risk in offspring. The positive association to lymphoma may be by chance and needs confirmation.

Fear of cancer recurrence among young adult cancer survivors-exploring long-term contributing factors in a large, population-based cohort.

PURPOSE: Fear of cancer recurrence (FCR) may be debilitating, yet knowledge of FCR among the growing population of long-term young adult cancer survivors (YACS) is scarce. We explored risk of FCR and associated factors in a nation-wide, population-based cohort of YACS. METHODS: All 5-year survivors diagnosed at the ages of 19-39 years with breast cancer (BC), malignant melanoma (MM), colorectal cancer (CRC), leukemia (LEU), or non-Hodgkin lymphoma (NHL) between 1985 and 2009 in Norway were identified by the Cancer Registry of Norway and completed the cross-sectional comprehensive NOR-CAYACS health survey. Univariate and multivariate linear regression modeling was performed. RESULTS: In total, 936 survivors were included, with an average of 16 years since diagnoses. BC was the most prevalent cancer form (38.4%), followed by MM (24.7%), NHL (15.6%), CRC (11.8%), and LEU (9.6%). Survivors worried most about getting another cancer (74%), and (20%) reported quite a bit or a lot of FCR. BC and MM survivors had the highest FCR scores. Post-traumatic stress symptoms (PTSS) had the strongest association with FCR (Std B 0.21, p < 0.01), above demographic and clinical variables. CONCLUSIONS: FCR is prevalent even among long-term YACS, including survivors of MM with favorable prognoses. IMPLICATIONS FOR CANCER SURVIVORS: Attention to ongoing risks of PTSS and FCR in this growing survivor population is warranted to optimize future survivorship care.

Non-steroidal anti-inflammatory drugs: use and co-treatment with potentially interacting medications in the elderly.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the elderly. NSAIDs may cause a series of adverse drug reactions, of which gastrointestinal, renovascular/cardiovascular and bleeding complications are of particular concern. Concomitant use of several other drugs may further increase the risk of these adverse effects. OBJECTIVE: To examine the extent of chronic use of NSAIDs and co-prescription of drugs which may seriously interact with NSAIDs in elderly subjects, by using data from the Norwegian Prescription Database. RESULTS: A total of 7.3% of all individuals (71,681/984,457) over 60 years of age filled at least one prescription for reimbursed NSAIDs during the 1-year study period (2006). Co-prescription of medications which may interact with NSAIDs was prevalent for drugs used for hypertension and/or heart failure (59.5%), antithrombotic drugs (35.1%), systemic glucocorticoids (12.9%) and SSRI antidepressants (8.3%). As many as 4.8 and 3.8% of NSAID users were co-prescribed warfarin or oral methotrexate respectively. CONCLUSION: The frequent co-prescription of medications which may cause detrimental interactions in elderly chronic NSAID users adds to safety concerns regarding this widely prescribed class of drugs.