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

Intraoperative Multispectral Fluorescence Imaging for the Detection of the Sentinel Lymph Node in Cervical Cancer: A Novel Concept

PURPOSE: Real-time intraoperative near-infrared fluorescence (NIRF) imaging is a promising technique for lymphatic mapping and sentinel lymph node (SLN) detection. The purpose of this technical feasibility pilot study was to evaluate the applicability of NIRF imaging with indocyanin green (ICG) for the detection of the SLN in cervical cancer. PROCEDURES: In ten patients with early stage cervical cancer, a mixture of patent blue and ICG was injected into the cervix uteri during surgery. Real-time color and fluorescence videos and images were acquired using a custom-made multispectral fluorescence camera system. RESULTS: Real-time fluorescence lymphatic mapping was observed in vivo in six patients; a total of nine SLNs were detected, of which one (11%) contained metastases. Ex vivo fluorescence imaging revealed the remaining fluorescent signal in 11 of 197 non-sentinel LNs (5%), of which one contained metastatic tumor tissue. None of the non-fluorescent LNs contained metastases. CONCLUSIONS: We conclude that lymphatic mapping and detection of the SLN in cervical cancer using intraoperative NIRF imaging is technically feasible. However, the technique needs to be refined for full applicability in cervical cancer in terms of sensitivity and specificity

The effect of tidal forcing on biogeochemical processes in intertidal salt marsh sediments

<p>Abstract</p> <p>Background</p> <p>Early diagenetic processes involved in natural organic matter (NOM) oxidation in marine sediments have been for the most part characterized after collecting sediment cores and extracting porewaters. These techniques have proven useful for deep-sea sediments where biogeochemical processes are limited to aerobic respiration, denitrification, and manganese reduction and span over several centimeters. In coastal marine sediments, however, the concentration of NOM is so high that the spatial resolution needed to characterize these processes cannot be achieved with conventional sampling techniques. In addition, coastal sediments are influenced by tidal forcing that likely affects the processes involved in carbon oxidation.</p> <p>Results</p> <p>In this study, we used in situ voltammetry to determine the role of tidal forcing on early diagenetic processes in intertidal salt marsh sediments. We compare ex situ measurements collected seasonally, in situ profiling measurements, and in situ time series collected at several depths in the sediment during tidal cycles at two distinct stations, a small perennial creek and a mud flat. Our results indicate that the tides coupled to the salt marsh topography drastically influence the distribution of redox geochemical species and may be responsible for local differences noted year-round in the same sediments. Monitoring wells deployed to observe the effects of the tides on the vertical component of porewater transport reveal that creek sediments, because of their confinements, are exposed to much higher hydrostatic pressure gradients than mud flats.</p> <p>Conclusion</p> <p>Our study indicates that iron reduction can be sustained in intertidal creek sediments by a combination of physical forcing and chemical oxidation, while intertidal mud flat sediments are mainly subject to sulfate reduction. These processes likely allow microbial iron reduction to be an important terminal electron accepting process in intertidal coastal sediments.</p

Controversies surrounding human papilloma virus infection, head & neck vs oral cancer, implications for prophylaxis and treatment

Head & Neck Cancer (HNC) represents the sixth most common malignancy worldwide and it is historically linked to well-known behavioural risk factors, i.e., tobacco smoking and/or the alcohol consumption. Recently, substantial evidence has been mounting that Human Papillomavirus (HPV) infection is playing an increasing important role in oral cancer. Because of the attention and clamor surrounding oral HPV infection and related cancers, as well as the use of HPV prophylactic vaccines, in this invited perspective the authors raise some questions and review some controversial issues on HPV infection and its role in HNC, with a particular focus on oral squamous cell carcinoma

The Musicality of Non-Musicians: An Index for Assessing Musical Sophistication in the General Population

Musical skills and expertise vary greatly in Western societies. Individuals can differ in their repertoire of musical behaviours as well as in the level of skill they display for any single musical behaviour. The types of musical behaviours we refer to here are broad, ranging from performance on an instrument and listening expertise, to the ability to employ music in functional settings or to communicate about music. In this paper, we first describe the concept of ‘musical sophistication’ which can be used to describe the multi-faceted nature of musical expertise. Next, we develop a novel measurement instrument, the Goldsmiths Musical Sophistication Index (Gold-MSI) to assess self-reported musical skills and behaviours on multiple dimensions in the general population using a large Internet sample (n = 147,636). Thirdly, we report results from several lab studies, demonstrating that the Gold-MSI possesses good psychometric properties, and that self-reported musical sophistication is associated with performance on two listening tasks. Finally, we identify occupation, occupational status, age, gender, and wealth as the main socio-demographic factors associated with musical sophistication. Results are discussed in terms of theoretical accounts of implicit and statistical music learning and with regard to social conditions of sophisticated musical engagement

Hint of an exocomet transit in the CHEOPS light curve of HD 172555

HD 172555 is a young (~20 Myr) A7V star surrounded by a 10 au wide debris disk suspected to be replenished partly by collisions between large planetesimals. Small evaporating transiting bodies, that is exocomets, have also been detected in this system by spectroscopy. After β Pictoris, this is another example of a system possibly witnessing a phase of the heavy bombardment of planetesimals. In such a system, small bodies trace dynamical evolution processes. We aim to constrain their dust content by using transit photometry. We performed a 2-day-long photometric monitoring of HD 172555 with the CHEOPS space telescope in order to detect shallow transits of exocomets with a typical expected duration of a few hours. The large oscillations in the light curve indicate that HD 172555 is a δ Scuti pulsating star. After removing those dominating oscillations, we found a hint of a transient absorption. If fitted with an exocomet transit model, it would correspond to an evaporating body passing near the star at a distance of 6.8±1.4R★ (or 0.05±0.01 au) with a radius of 2.5 km. These properties are comparable to those of the exocomets already found in this system using spectroscopy, as well as those found in the β Pic system. The nuclei of the Solar System's Jupiter family comets, with radii of 2-6 km, are also comparable in size. This is the first piece of evidence of an exocomet photometric transit detection in the young system of HD 172555

Differences in Mammographic Density Decline over Time in Breast Cancer Cases and Women at High Risk for Breast Cancer

Abstract Introduction: High absolute breast density and increased breast density over time are strongly associated with breast cancer risk, and breast density generally decreases with increasing age. We examined mammographic density data from members of the Women At Risk High-Risk Registry at Columbia University Medical Center (WAR), a cohort defined as at high risk for breast cancer due to family history of breast cancer, history of lobular carcinoma in situ, and/or benign breast disease, to determine changes in their breast density over time. Methods: Within the WAR cohort of 1598 women, we conducted a nested case-control study of 66 incident cases of invasive breast cancer and 70 women without cancer, matched on age and time between first and second mammogram. For each participant, we collected two mammograms (for the cases, both mammograms occurred before cancer diagnosis), to examine differences in absolute density, percent density, and change in density between cases and controls. The average time between first and second mammogram was 4.6 years for both cases and controls, with a range of between 1 and 15 years. Results: Using linear regression with change in percent density as the outcome, and time between first and second mammogram as the independent variable, we found that among women without breast cancer, density decreased as time between first and second mammogram increased (β = −2.15, p = 0.005). In contrast, there was no overall change in density among the cases associated with time between first and second mammogram (β = 0.69, p = 0.39). In an ANCOVA comparing the slopes of the regression lines, the slopes were significantly different for cases versus controls (p = 0.009). Conclusion: In a cohort of women at high risk for breast cancer, breast density does not decrease as time between mammograms increases, for women who go on to develop breast cancer. For women who do not develop breast cancer, breast density decreases significantly over time.</jats:p

P4-11-06: Uptake of Selective Estrogen Receptor Modulators and Other Breast Cancer Prevention Strategies among High-Risk Women Seen in a Breast Center.

Abstract Background: Selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, are FDA-approved for breast cancer (BC) risk reduction. However, uptake has been poor in the prevention setting, partly due to a lack of knowledge in the medical community about BC prevention and public misconceptions about the risks of SERMs. We assessed demographic and clinical factors that influence SERM uptake among high-risk women seen in an academic breast center, where specialized risk counseling is provided by a breast surgeon or medical oncologist. Methods: Potential subjects included high-risk women seen for an initial consultation by Breast Surgery or Medical Oncology. Eligibility for SERM use included a 5-year Gail risk ≥1.67%, lobular carcinoma in situ (LCIS), BRCA mutation carrier, or estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive ductal carcinoma in situ (DCIS). Demographic and BC risk factor data was collected from self-administered questionnaires. Clinical data, including prior/current SERM use, was abstracted from medical chart review. Differences in distribution of risk factors, between women who ever took a SERM and those who did not, were examined using chi-square statistics or Fisher's exact test. Multivariable logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals using SERM use as the dependent variable. Results: Among 247 high-risk women enrolled between March 2007 and January 2011, median age 51 (17-82); White/Hispanic/Black/Asian (%): 55/32/7/6. 85% of women were undergoing annual mammography, 94% had a breast biopsy, 19% genetic testing, and 71% Medical Oncology referral. Among 181 (73%) women eligible for a SERM, Gail risk ≥1.67%/LCIS/DCIS/BRCA mutation (%): 35/22/39/3; 83 (46%) ever took a SERM, including 62 on tamoxifen and 21 on raloxifene. Early SERM discontinuation was only 7%. In multivariable analysis, significant predictors of SERM uptake included risk category (DCIS vs. Gail risk ≥1.67%/LCIS/BRCA mutation), higher income, higher body mass index (BMI), and referral to Medical Oncology. In terms of this high-risk population meeting American Cancer Society (ACS) behavioral guidelines for cancer prevention, 53% had a BMI &amp;lt;25 kg/m2, 44% consumed ≤1 alcoholic beverage per day, and 10% engaged in ≥4 hours of moderate physical activity per week; only 3.5% met all 3 recommendations. Conclusions: Among high-risk women seen at a specialized breast center, application of clinical recommendations such as screening mammography, genetic testing, and SERM uptake were relatively high, suggesting that a comprehensive approach to the management of high-risk women is feasible. However, meeting ACS nutrition and physical activity guidelines for cancer prevention was limited, perhaps due to a lack of reimbursable staff to implement these guidelines. Breast cancer risk assessment and available interventions for prevention among high-risk women are underutilized in the U.S. Future studies should focus on the development and delivery of breast cancer prevention strategies. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-06.</jats:p