Identification of women with an increased risk of developing radiation-induced breast cancer

In the previous issue of Breast Cancer Research, Broeks and collaborators present the results of a study suggesting that germline mutations in BRCA1, BRCA2, ATM or CHEK2 may double the risk of radiation-induced contralateral breast cancer following radiotherapy for a first breast cancer. The assocation appeared to be strongest among women who were below the age of 40 at the time of their first breast cancer and among women who developed their second cancer 5 years or more after the first. While there were a number of methodological issues that might limit the conclusions drawn from this paper, this is one of several recent studies suggesting that carriers of pathogenic alleles in DNA repair and damage recognition genes may have an increased risk of breast cancer following exposure to ionising radiation, even at low doses. This finding has important implications for the protection of breast cancer patients and their close relatives. If confirmed, mutation carriers may wish to consider alternatives to X-ray for diagnostic purposes. The need for tailored cancer treatment strategies in carriers should also be evaluated carefully

Adjuvant radiotherapy for primary breast cancer in BRCA1 and BRCA2 mutation carriers and risk of contralateral breast cancer with special attention to patients irradiated at younger age

The purpose of this study was to estimate the influence of adjuvant radiotherapy for primary breast cancer (BC) on the risk of contralateral BC (CBC) in BRCA1 or BRCA2(BRCA1/2) mutation carriers, with special attention to patients irradiated at age younger than 40 years. Additionally, tendencies in locoregional treatments and rates of contralateral risk-reducing mastectomy over time were explored. In this retrospective cohort study, 691 BRCA1/2-associated BC patients treated between 1980 and 2013 were followed from diagnosis until CBC or censoring event including ipsilateral BC recurrence, distant metastasis, contralateral risk-reducing mastectomy, other invasive cancer diagnosis, death, or loss to follow up. Hazard ratios (HR) for CBC associated with radiotherapy were estimated using Cox regression. Median follow-up time was 8.6 years [range 0.3–34.3 years]. No association between radiotherapy for primary BC and risk of CBC was found, neither in the total population (HR 0.82, 95 % CI 0.45–1.49) nor in the subgroup of patients younger than 40 years at primary diagnosis (HR 1.36, 95 % CI 0.60–3.09). During follow-up, the number of patients at risk decreased substantially since a large proportion of patients were censored after contralateral risk-reducing mastectomy or BC recurrence. Over the years, increasing preference for mastectomy without radiotherapy compared to breast-conserving surgery with radiotherapy was found ranging from less than 30 % in 1995 to almost 50 % after 2010. The rate of contralateral risk-reducing mastectomy increased over the years from less than 40 % in 1995 to more than 60 % after 2010. In this cohort of BRCA1/2-associated BC patients, no association between radiotherapy for primary BC and risk of CBC was observed in the total group, nor in the patients irradiated before the age of 40 years. The number of patients at risk after 10 and 15 years of follow-up, however, was too small to definitively exclude harmful effects of adjuvant radiotherapy

Pediatric Differentiated Thyroid Carcinoma in The Netherlands: A Nationwide Follow-Up Study

Introduction: Treatment for differentiated thyroid carcinoma (DTC) in pediatric patients is based mainly on evidence from adult series due to lack of data from pediatric cohorts. Our objective was to evaluate presentation, treatment-related complications, and long-term outcome in patients with pediatric DTC in the Netherlands. Patients and methods: In this nationwide study, presentation, complications and outcome of patients with pediatric DTC (age at diagnosis ≤18 years) treated in the Netherlands between 1970 and 2013 were assessed using medical records. Results: We identified 170 patients. Overall survival was 99.4% after median follow-up of 13.5 (range 0.3–44.7) years. Extensive follow-up data were available for 105 patients (83.8% women), treated in 39 hospitals. Median age at diagnosis was 15.6 (range 5.8–18.9) years. At initial diagnosis, 43.8% of the patients had cervical lymph node metastases; 13.3% had distant metastases. All patients underwent total thyroidectomy. Radioiodine was administered to 97.1%, with a median cumulative activity of 5.66 (range 0.74–35.15) GBq. Lifelong postoperative complications (permanent hypoparathyroidism and/or recurrent laryngeal nerve injury) were present in 32.4% of the patients. At last known follow-up, 8.6% of the patients had persistent disease and 7.6% experienced a recurrence. TSH suppression was not associated with recurrences (OR 2.00, 95% CI 0.78 to 5.17, P = 0.152). Conclusions: Survival of pediatric DTC is excellent. Therefore, minimizing treatment-related morbidity takes major priority. Our study shows a frequent occurrence of lifelong postoperative complications. Adverse effects may be reduced by centralization of care, which is crucial for children with DTC

Risk Factors for Nonsynchronous Second Primary Malignancy and Related Death in Patients with Differentiated Thyroid Carcinoma

BACKGROUND: Differentiated thyroid cancer (DTC) survivors are at increased risk of developing nonsynchronous second primary malignancy (NSPM). This study aims to examine possible risk factors leading to occurrence of NSPM as well as risk factors leading to NSPM-related death in patients with DTC. METHODS: Of the 1,106 patients with DTC managed at our institution, 92 (8.3%) patients developed NSPM and 40 (3.6%) patients died of NSPM. All causes of death were confirmed by medical record, autopsy report or death certificate. Clinicopathological variables were compared between those without NSPM and with NSPM as well as between those who died of NSPM and did not die of NSPM. Significant variables on univariate analysis were entered into a Cox proportional hazards model. RESULTS: The median latency period from diagnosis of DTC to NSPM was 142.7 (range 16.8-511.0) months. For occurrence of NSPM, age at DTC diagnosis >/=50 years old [relative risk (RR) = 2.35], cumulative radioactive iodine (RAI) activity 3.0-8.9 GBq (RR = 2.38), and external local radiotherapy (ERT) (RR = 1.95) were significant risk factors. For NSPM-related death, age at DTC diagnosis >/=50 years old (RR = 3.32) and nonbreast cancer (RR = 5.76) were significant risk factors. CONCLUSIONS: NSPM accounted for 18.7% of all deaths in DTC, but mortality was high (43.5%). Age at DTC diagnosis >/=50 years old, cumulative RAI activity 3.0-8.9 GBq, and ERT were significant risk factors for occurrence of NSPM, whereas age at DTC diagnosis >/=50 years old and the diagnosis of nonbreast cancer were significant risk factors for NSPM-related death.published_or_final_versionSpringer Open Choice, 21 Feb 201

Program design features that can improve participation in health education interventions

<p>Abstract</p> <p>Background</p> <p>Although there have been reported benefits of health education interventions across various health issues, the key to program effectiveness is participation and retention. Unfortunately, not everyone is willing to participate in health interventions upon invitation. In fact, health education interventions are vulnerable to low participation rates. The objective of this study was to identify design features that may increase participation in health education interventions and evaluation surveys, and to maximize recruitment and retention efforts in a general ambulatory population.</p> <p>Methods</p> <p>A cross-sectional questionnaire was administered to 175 individuals in waiting rooms of two hospitals diagnostic centres in Toronto, Canada. Subjects were asked about their willingness to participate, in principle, and the extent of their participation (frequency and duration) in health education interventions under various settings and in intervention evaluation surveys using various survey methods.</p> <p>Results</p> <p>The majority of respondents preferred to participate in one 30–60 minutes education intervention session a year, in hospital either with a group or one-on-one with an educator. Also, the majority of respondents preferred to spend 20–30 minutes each time, completing one to two evaluation surveys per year in hospital or by mail.</p> <p>Conclusion</p> <p>When designing interventions and their evaluation surveys, it is important to consider the preferences for setting, length of participation and survey method of your target population, in order to maximize recruitment and retention efforts. Study respondents preferred short and convenient health education interventions and surveys. Therefore, brevity, convenience and choice appear to be important when designing education interventions and evaluation surveys from the perspective of our target population.</p

Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study

Introduction: Radiation exposure at a young age is one of the strongest risk factors for breast cancer. Germline mutations in genes involved in the DNA-damage repair pathway (DDRP) may render women more susceptible to radiation-induced breast cancer. Methods: We evaluated the contribution of germline mutations in the DDRP genes BRCA1, BRCA2, CHEK2 and ATM to the risk of radiation-induced contralateral breast cancer (CBC). The germline mutation frequency was assessed, in a case-only study, in women who developed a CBC after they had a first breast cancer diagnosed before the age of 50 years, and who were (n = 169) or were not (n = 78) treated with radiotherapy for their first breast tumour. Results: We identified 27 BRCA1, 5 BRCA2, 15 CHEK2 and 4 truncating ATM germline mutation carriers among all CBC patients tested (21%). The mutation frequency was 24.3% among CBC patients with a history of radiotherapy, and 12.8% among patients not irradiated for the first breast tumour (odds ratio 2.18 (95% confidence interval 1.03 to 4.62); p = 0.043). The association between DDRP germline mutation carriers and risk of radiation-induced CBC seemed to be strongest in women who developed their second primary breast tumour at least 5 years after radiotherapy. Th