Normal tissue complication probability models in plan evaluation of children with brain tumors referred to proton therapy.

Background: Children with brain tumors undergoing radiotherapy are at particular risk of radiation-induced morbidity and are therefore routinely considered for proton therapy (PT) to reduce the dose to healthy tissues. The aim of this study was to apply pediatric constraints and normal tissue complication probability (NTCP) models when evaluating the differences between PT and contemporary photon-based radiotherapy, volumetric modulated arc therapy (VMAT). Methods: Forty patients (aged 1-17 years) referred from Norwegian institutions to cranial PT abroad during 2014-2016 were selected for VMAT re-planning using the original CT sets and target volumes. The VMAT and delivered PT plans were compared by dose/volume metrics and NTCP models related to growth hormone deficiency, auditory toxicity, visual impairment, xerostomia, neurocognitive outcome and secondary brain and parotid gland cancers. Results: The supratentorial brain, temporal lobes, hippocampi, hypothalamus, pituitary glands, cochleas, salivary glands, optic nerves and chiasm received lower mean doses from PT. Reductions in population median NTCP were significant for auditory toxicity (VMAT: 3.8%; PT: 0.3%), neurocognitive outcome (VMAT: 3.0 IQ points decline at 5 years post RT; PT: 2.5 IQ points), xerostomia (VMAT: 2.0%; PT: 0.6%), excess absolute risk of secondary cancer of the brain (VMAT: 9.2%; PT: 6.7%) and salivary glands (VMAT: 2.8%; PT:0.5%). Across all patients, 23/38 PT plans had better or comparable estimated risks for all endpoints (within ±10% of the risk relative to VMAT), whereas for 1/38 patients all estimates were better or comparable with VMAT. Conclusions: PT reduced the volumes of normal tissues exposed to radiation, particularly low-to-intermediate dose levels, and this was reflected in lower NTCP. Of the included endpoints, substantial reductions in population medians were seen from the delivered PT plans for auditory complications, xerostomia, and risk of secondary cancers of the brain and salivary glands.

Anthropometric factors and risk of molecular breast cancer subtypes among postmenopausal Norwegian women.

Adult height and body weight are positively associated with breast cancer risk after menopause, but few studies have investigated these factors according to molecular breast cancer subtype. A total of 18,562 postmenopausal Norwegian women who were born between 1886 and 1928 were followed up for breast cancer incidence from the time (between 1963 and 1975) height and weight were measured until 2008. Immunohistochemical and in situ hybridization techniques were used to subtype 734 incident breast cancer cases into Luminal A, Luminal B [human epidermal growth factor receptor 2 (HER2-)], Luminal B (HER2+), HER2 subtype, basal-like phenotype (BP) and five-negative phenotype (5NP). We used Cox regression analysis to assess adult height and body mass index (BMI) in relation to risk of these subtypes. We found a positive association of height with risk of Luminal A breast cancer (ptrend , 0.004), but there was no clear association of height with any other subtype. BMI was positively associated with risk of all luminal breast cancer subtypes, including Luminal A (ptrend , 0.002), Luminal B (HER2-) (ptrend , 0.02), Luminal B (HER2+) (ptrend , 0.06), and also for the HER2 subtype (ptrend , 0.04), but BMI was not associated with risk of the BP or 5NP subtypes. Nonetheless, statistical tests for heterogeneity did not provide evidence that associations of height and BMI differed across breast cancer subtypes. This study of breast cancer risk among postmenopausal women suggests that height is positively associated with risk of Luminal A breast cancer. BMI is positively associated with risk of all luminal subtypes and for the HER2 subtype.

Association of time since last birth, age at first birth and parity with breast cancer survival among parous women: a register-based study from Norway.

Reproductive factors that have a well-documented effect on breast cancer risk may also influence the prognosis of the disease, but previous studies on breast cancer survival have yielded conflicting results. We combined information from two population-based registries and obtained information on 16,970 parous women with invasive breast cancer. Cox regression analysis was used to assess breast cancer survival in relation to age at diagnosis, age at first birth, time since last birth and parity. We stratified the analyses by age at diagnosis (<50 and ≥ 50 years) as an approximation for menopausal age. In women diagnosed before 50 years of age, breast cancer survival was reduced with younger age at diagnosis (p for trend <0.001), whereas in women diagnosed at 50 years or later, survival was reduced with older age at diagnosis (p for trend 0.011). For breast cancer diagnosed before 50 years, survival was poorer in women with four or more births compared to women with one or two births (hazard ratio 1.3, 95% confidence interval 1.1-1.6). A short time since last birth was associated with reduced survival (p for trend 0.05), but adjustment for stage and grade attenuated the association. Among women diagnosed at 50 years or later, we found no association with survival for any of the reproductive factors. In summary, reproductive factors were associated with survival from breast cancer diagnosed before but not after age 50 years. Young women had a particularly poor prognosis throughout the study period.

Placental weight and breast cancer risk in young women: a registry-based cohort study from Norway.

BACKGROUND: Pregnancy has a short-term risk-increasing effect on breast cancer that may be attributed to growth-promoting effects of pregnancy hormones on prevalent but undetected tumors. Results of two previous studies suggested that placental weight may be positively associated with breast cancer risk. METHODS: In a cohort of 338,051 women followed from 1999 to 2008, on the basis of data linkage between the Medical Birth Registry of Norway and the Cancer Registry of Norway, we assessed whether placental weight in a woman's most recent pregnancy was related to breast cancer risk during the first years following pregnancy. RESULTS: During follow-up (median, 6.0 years; interquartile range, 3.0-8.3 years), 648 women were diagnosed with breast cancer at a mean age of 38.4 years (standard deviation, 5.3 years). Placental weight in the most recent pregnancy was not associated with breast cancer risk: the hazard ratio per 100-gram increase in placental weight was 1.03 [95% confidence interval, 0.96-1.10]. There was a similar lack of association related to mean placental weight across pregnancies and to placental weight associated with the first birth. CONCLUSION: We could not confirm previous reports that women who develop large placentas are at increased risk of breast cancer. IMPACT: The epidemiologic support for an association of placental weight with breast cancer risk remains inconclusive. More research is needed to identify factors that influence breast cancer risk in young women.

The association of reproductive factors and breastfeeding with long term survival from breast cancer.

Reproductive factors that influence breast cancer risk may also have an impact on survival, once the disease is diagnosed. In this study, 2,640 women were diagnosed with invasive breast cancer during follow-up after a breast cancer screening that took place in 1956-1959. Survival was assessed in relation to age at menarche, age at first birth, parity, history of breastfeeding, age at menopause, and the effect of BMI was assessed in a subset of patients. It is a special feature that the patients of this study have not been subjected to organized mammography screening and their use of exogenous hormones has been negligible. By the end of follow-up (2008), 2,301 (87%) of the patients had died and 1,022 (44%) of the deaths were caused by breast cancer. Breast cancer survival was not associated with age at menarche, parity or time since last birth, but survival was consistently poorer with increasing age at first birth (P for trend 0.03): comparing a first birth after 35 years with 25-29 years, the hazard ratio was 1.32 (95% CI 1.02-1.72). There was no evidence for a dose-related effect of breastfeeding, but BMI measured many years prior to diagnosis was inversely associated with survival (P for trend <0.01). The main finding was that reproductive factors, including breastfeeding, appear to have little influence on the survival of breast cancer patients. Age at first birth may be an exception to this, since we found a gradually poorer survival with increasing age at first birth. We also found that overweight and obesity, as measured many years prior to diagnosis, were associated with poorer survival.