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BackgroundAlthough the timing of pubertal milestones has been associated with breast cancer risk, few studies of girls' development include girls at increased breast cancer risk due to their family history.MethodsThe Lessons in Epidemiology and Genetics of Adult Cancer from Youth (LEGACY) Girls Study was initiated in 2011 in the USA and Canada to assess the relation between early life exposures and intermediate markers of breast cancer risk (e.g., pubertal development, breast tissue characteristics) and to investigate psychosocial well being and health behaviors in the context of family history. We describe the methods used to establish and follow a cohort of 1,040 girls ages 6-13 years at baseline, half with a breast cancer family history, and the collection of questionnaire data (family history, early life exposures, growth and development, psychosocial and behavioral), anthropometry, biospecimens, and breast tissue characteristics using optical spectroscopy.ResultsDuring this initial 5-year phase of the study, follow-up visits are conducted every 6 months for repeated data and biospecimen collection. Participation in baseline components was high (98% for urine, 97.5% for blood or saliva, and 98% for anthropometry). At enrollment, 77% of girls were premenarcheal and 49% were at breast Tanner stage T1.ConclusionsThis study design allows thorough examination of events affecting girls' growth and development and how they differ across the spectrum of breast cancer risk. A better understanding of early life breast cancer risk factors will be essential to enhance prevention across the lifespan for those with and without a family history of the disease.

Background: Tanner staging (TS), a five-stage classification indicating no breast tissue (TS1) to full breast development (TS5), is used both in health research and clinical care to assess the onset of breast development (TS2) and duration in each stage. Currently, TS is measured both visually and through palpation but non-invasive methods will improve comparisons across settings.Methods: We used optical spectroscopy (OS) measures from 102 girls at the Ontario site of the LEGACY girls study (average age 12 years, range 10.0-15.4 years) to determine whether breast tissue optical properties map to each TS. We further examined whether these properties differed by age, body mass index (BMI), and breast cancer risk score (BCRS) by examining the major principal components (PC).Results: Age and BMI increased linearly with increasing TS. Eight PCs explained 99.9% of the variation in OS data. Unlike the linear increase with age and BMI, OS components had distinct patterns by TS: the onset of breast development (TS1 to TS2) was marked by elevation of PC3 scores indicating an increase in adipose tissue and decrease in signal from the pectoral muscle; transition to TS3 was marked by elevation of PC6 and PC7 and decline of PC2 scores indicating an increase in glandular or dense tissue; and transition to TS4+ by decline of PC2 scores representing a further increase in glandular tissue relative to adipose tissue. Of the eight PCs, three component scores (PC4, PC5, and PC8) remained in the best-fitting model of BCRS, suggesting different levels of collagen in the breast tissue by BCRS.Conclusions: Our results suggest that serial measures of OS, a non-invasive assessment of breast tissue characteristics, can be used as an objective outcome that does not rely on visual inspection or palpation, for studying drivers of breast development. [ABSTRACT FROM AUTHOR]

Medical laser applications based on widespread research and development is a very dynamic and increasingly popular field from an ecological as well as an economic point of view. Conferences and personal communication are necessary to identify specific requests and potential unmet needs in this multi- and interdisciplinary discipline. Precise gathering of all information on innovative, new, or renewed techniques is necessary to design medical devices for introduction into clinical applications and finally to become established for routine treatment or diagnosis. Five examples of successfully addressed clinical requests are described to show the long-term endurance in developing light-based innovative clinical concepts and devices. Starting from laboratory medicine, a noninvasive approach to detect signals related to iron deficiency is shown. Based upon photosensitization, fluorescence-guided resection had been discovered, opening the door for photodynamic approaches for the treatment of brain cancer. Thermal laser application in the nasal cavity obtained clinical acceptance by the introduction of new laser wavelengths in clinical consciousness. Varicose veins can be treated by innovative endoluminal treatment methods, thus reducing side effects and saving time. Techniques and developments are presented with potential for diagnosis and treatment to improve the clinical situation for the benefit of the patient. [ABSTRACT FROM AUTHOR]

Purpose: Variations during breast tissue development can influence later breast cancer risk. In particular, prolonged nulliparity increases risk. The authors used optical spectroscopy to compare breast tissue in 115 nulliparous women aged 31–40 (group 2) to 140 nulliparous women aged 18–21 (group 1), and also to 36 parous women aged 31–40 (group 3), and to evaluate the relationship between IGF-1 and optical breast tissue properties. IGF-1 has been linked in particular to premenopausal breast cancer. Methods: The authors measured the transmission spectra from 625 to 1050 nm wavelengths in each breast and determined regions of interindividual variation using principal components analysis. Spectral differences represent variation in lipid, water, oxyhemoglobin, deoxyhemoglobin, and collagen content. Group differences and the relationship with IGF-1 were estimated by linear regression after adjustment for multiple factors including height, weight, ethnicity, hormonal contraceptive use, and days since last menstrual period. Results: Principal component 3 scores were more negative in the older nulliparous women compared to either younger nulliparous women or to parous women of the same age (β=-0.16, p=0.008 for group 2 vs group 1 and β=0.51, p=0.03 for group 3 vs group 2). These differences appear to indicate increased deoxyhemoglobin relative to oxyhemoglobin content in the tissue of the older, nulliparous premenopausal women compared to the other groups, which may be an indicator of proportionally increased proliferative tissue. Principal component 4 also differed between older and younger nulliparous women (β=0.08, p=0.02 for group 2 vs group 1) and was negatively associated with IGF-1 in younger women (β=-0.0004, p=0.03) and positively associated with IGF-1 in older women (β=0.001, p=0.004). Conclusions: Optical spectroscopy may be useful to identify breast tissue at increased risk of cancer development and track changes over time, particularly in young women where exposure to radiation is of particular concern. Additional work is needed to confirm the observed breast tissue differences and to determine the specific tissue chromophore changes with age and parity. [ABSTRACT FROM AUTHOR]

Photodynamic therapy has been successfully applied to numerous cancers. Its potential to treat cancer metastases in the spine has been demonstrated previously in a preclinical animal model. The aim of this study was to test two photosensitizers, benzoporphyrin-derivative monoacid ring A (BPD-MA) and by 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), for their potential use to treat bony metastases. The difference in photosensitizer concentration in the spinal cord and the surrounding tumor-bearing vertebrae was of particular interest to assess the risk of potential collateral damage to the spinal cord. Vertebral metastases in a rat model were generated by intracardiac injection of human breast cancer cells. When tumor growth was confirmed, photosensitizers were injected systemically and the animals were euthanized at different time points. The following tissues were harvested: liver, kidney, ovaries, appendicular bone, spinal cord and lumbar vertebrae. Photosensitizer tissue concentration of BPD-MA or PpIX was determined by fluorescence spectrophotometry. In contrast to BPD-MA, ALA-PpIX did not demonstrate an appreciable difference in the uptake ratio in tumor-bearing vertebrae compared to spinal cord. The highest ratio for BPD-MA concentration was found 15 min after injection, which can be recommended for therapy in this model. [ABSTRACT FROM AUTHOR]