Search

Purpose: Nipple aspiration fluid (NAF) is a non-invasively-acquired biosample that can provide a window into the breast environment, but NAF yield is highly variable. Its determinants must be better understood for studies of breast cancer risk. The wet earwax phenotype was identified as one determinant of NAF yield in the 1970s, and is linked to single nucleotide polymorphisms (SNPs) in the ATP-binding cassette transporter gene ABCC11. We have investigated this, as well as SNPs in the prolactin (PRL) and prolactin receptor (PRLR) genes, in relation to NAF yield., Methods: DNA was extracted from white blood cells of 557 NAF yielders and 359 non-yielders, and was used to genotype ABCC11 (rs17822931), PRL (rs849870, rs849872, rs849886, rs2244502, rs1341239), and PRLR (rs37364, rs34024951, rs1610218, rs9292575, rs7718468) using Taqman genotyping assay. The association between NAF yield and each single SNP was analyzed using logistic regression adjusting for age, race, and menopausal status., Results: ABCC11 rs17822931 showed a negative association with NAF yield [odds ratio (OR) 0.66, 95 % confidence interval (CI) 0.49-0.88; p = 0.004]. The PRL rs849870 and the haplotype combination with other SNPs showed a marginal association with NAF yield. In addition, the years since last birth also showed negative association with NAF yielding (OR 0.98, 95 % CI 0.96-0.99; p = 0.001). The combination of the years since last birth with ABCC11 SNP revealed significant interaction between reproductive factor and genetic factor., Conclusions: Our results confirmed the association between NAF yield and earwax phenotype through ABCC11 genotype. Combined with the recency of last birth, ABCC11 genotype should be considered in the design of studies utilizing NAF as a biosample.

Introduction: The accuracy of breast magnetic resonance imaging (MRI) for detection of ductal carcinoma in situ (DCIS) has prompted recommendations for its routine preoperative use, but its clinical benefit is debated. We reviewed our experience with MRI in DCIS patients to assess the utility of MRI for surgical planning., Methods: DCIS patients (2008-2010) were identified through a prospectively maintained database and grouped into MRI and no-MRI groups. The rates of additional biopsies, altered surgical management, and reoperation were compared. Additionally, DCIS size ascertained by mammography, MRI, and final pathology was compared., Results: Of 352 DCIS patients, 217 received MRI and 135 did not. The type of initial operation and number of reoperations were similar between the two groups, but successful breast conservation was more frequent in the no-MRI group (p = 0.06). The additional biopsy rate was 38 % in the MRI group versus 7 % in the no-MRI group; ≥2 additional biopsies were performed in 18 % of the MRI group and 2 % of the no-MRI group (p < 0.0001). These yielded a cancer diagnosis in 26 % of MRI and 33 % of no-MRI patients (p = 0.73). MRI was not superior to mammogram in detecting size of DCIS lesions preoperatively; 52 % of mammograms were accurate (within 1 cm) compared with 41 % of MRIs., Conclusions: DCIS patients who undergo preoperative breast MRI are far more likely to undergo additional biopsies. Unless these can be demonstrated to lead to improved long-term outcomes, the utility of routine preoperative MRI in DCIS patients remains questionable.

Background: Breast cancers (BCs) diagnosed after a recent pregnancy display features associated with poor prognosis, including hormone receptor negativity, but other tumor markers have not been examined. We sought to define the tumor marker profile of these cancers, including HER-2 and p53 expression, and examine the time interval over which this adverse profile is observed, relative to last pregnancy., Methods: A prospectively maintained database was reviewed to identify women with a BC diagnosis between 1998 to 2011. Parous women were categorized on the basis of the interval between pregnancy and BC diagnosis; 0-2 years, >2-5 years, >5-10 years, and >10-15 years. Tumor characteristics of parous cases were compared to those of nulliparous BC patients, who were frequency matched by age., Results: A total of 175 parous and 114 nulliparous women were identified. Women who were 0-2 years from last parity at the time of BC diagnosis were the only group who were more likely than control women to have grade 3 tumors (P<0.01), positive lymph nodes (P=0.02), and triple negative tumors (P=0.01, odds ratio 3.2, 95% confidence interval 1.2-8.5). There was no difference noted in HER-2 or p53 status relative to interval from pregnancy., Conclusions: BC diagnosed within 2 years of pregnancy is more likely to have poor prognostic features and to be triple negative. More work is needed to delineate the time frame of pregnancy-associated BC and to define them on a molecular level, so as to devise better prevention and therapy for this devastating problem.

Both treatment efficacy and safety are typically the primary endpoints in Phase II, and even in some Phase III, clinical trials. Efficacy is frequently measured by time to response, death, or some other milestone event and thus is a continuous, possibly censored, outcome. Safety, however, is frequently measured on a discrete scale; in Eastern Cooperative Oncology Group clinical trial E2290, it was measured as the number of weekly rounds of chemotherapy that were tolerable to colorectal cancer patients. For the joint analysis of efficacy and safety, we propose a non-parametric, computationally simple estimator for the bivariate survival function when one time-to-event is continuous, one is discrete, and both are subject to right-censoring. The bivariate censoring times may depend on each other, but they are assumed to be independent of both event times. We derive a closed-form covariance estimator for the survivor function which allows for inference to be based on any of several possible statistics of interest. In addition, we derive its covariance with respect to calendar time of analysis, allowing for its use in sequential studies.

Background: As behavioral health risks account for the major causes of preventable morbidity and mortality in the United States, national guidelines recommend that physicians routinely screen patients for risk factors, and counsel as appropriate., Objectives: To assess the scope of health risk screening and characterize the communication content of counseling for health behavior change in 2 general internal medicine practices., Design and Participants: We studied videotapes of 125 new patient visits to General Internists affiliated with academic medical centers in Chicago, IL (70%) and Burlington, VT (30%). All videotapes were content analyzed to examine (1) the incidence and outcome of screening for diet, exercise, tobacco, alcohol, drugs, sex, seatbelt use, helmet use, firearms, smoke detectors, and sun exposure; (2) the content of counseling for at-risk behaviors, with a focus on 11 counseling tasks associated with health behavior change., Results: Patient age in these 125 initial visits ranged from 22 to 85 years. Within the 91 visits that included at least 1 screening attempt, there were a total of 361 distinct screening discussions (mean=3.9, SD=2.2, range=1 to 9). Seventy-four (20.5%) of the 361 screening discussions revealed an at-risk behavior. On average, 2.4 of the 11 counseling tasks were accomplished for each of the 74 behavioral health risks (SD=2.2, range 0 to 9); only education about the problem (56.8%) and general advice about the solution (62.2%) were evident in more than half of the counseling attempts., Conclusions: This observational study reveals that communication tasks associated with successful counseling were relatively infrequent occurrences during initial visits in 2 primary care practices.