Citations

This paper begins with a patient perspective from the first author. Faced with cascading health problems, this author describes her gradual embrace of alternative treatments. While these improved her health, they also set her apart and prompted antagonism from those in conventional medicine. She found she was not alone in benefiting from a more open view of healing, and not alone in being buffeted by the opposing medical views. Two invited commentaries from medical professionals follow, as well as the first author’s response.

Abstract Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08–1.14, P = 7 × 10−18) for invasive breast cancer and 1.10 (95% CI = 1.01–1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99–1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12–1.20, P = 1 × 10−18 vs. OR = 1.03, 95% CI = 0.99–1.07, P = 0.2 for PR-negative disease; Pheterogeneity = 2 × 10−7); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14–1.25), 1.13 (1.09–1.16), and 1.04 (0.99–1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10−7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222–31. ©2011 AACR.

Prostate cancer is the second common cancer in men worldwide. The prevention of prostate cancer remains a challenge to researchers and clinicians. Here, we review the relationship of vitamin D and sunlight to prostate cancer risk. Ultraviolet radiation of the sunlight is the main stimulator for vitamin D production in humans. Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin D receptor (VDR), and VDR-regulated genes. Although laboratory studies including the use of animal models have shown that vitamin D has antiprostate cancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be inconclusive and an intensively studied subject. This review will provide up-to-date information regarding the recent outcomes of laboratory and epidemiology studies on the effects of vitamin D on prostate cancer prevention.

PurposeColorectal cancer predominantly occurs in the elderly, but approximately 5% of patients are 50 years old or younger. We sought to determine whether young age is prognostic, or whether it influences efficacy/toxicity of chemotherapy, in patients with advanced disease.MethodsWe analyzed individual data on 6,284 patients from nine phase III trials of advanced colorectal cancer (aCRC) that used fluorouracil-based single-agent and combination chemotherapy. End points included progression-free survival (PFS), overall survival (OS), response rate (RR), and grade 3 or worse adverse events. Stratified Cox and adjusted logistic-regression models were used to test for age effects and age-treatment interactions.ResultsA total of 793 patients (13%) were younger than 50 years old; 188 of these patients (3% of total patients) were younger than 40 years old. Grade 3 or worse nausea (10% v 7%; P = .01) was more common, and severe diarrhea (11% v 14%; P = .001) and neutropenia (23% v 26%; P < .001) were less common in young (younger than 50 years) than in older (older than 50 years) patients. Age was prognostic for PFS, with poorer outcomes occurring in those younger than 50 years (median, 6.0 v 7.5 months; hazard ratio, 1.10; P = .02), but it did not affect RR or OS. In the subset of monotherapy versus combination chemotherapy trials, the relative benefits of multiagent chemotherapy were similar for young and older patients. Results were comparable when utilizing an age cut point of 40 years.ConclusionYoung age is modestly associated with poorer PFS but not OS or RR in treated patients with aCRC, and young patients have more nausea but less diarrhea and neutropenia with chemotherapy in general. Young versus older patients derive the same benefits from combination chemotherapy. Absent results of a clinical trial, standard combination chemotherapy approaches are appropriate for young patients with aCRC.

Abstract Background Local recurrence after breast conservation surgery (BCS) varies with clinical risk factors. The aim of this study was to evaluate how local recurrence rates vary by patient age at time of BCS. Methods With IRB approval, all patients undergoing BCS for primary breast cancer between 1988 and 2001 at Mayo Clinic, Rochester were identified. Patients receiving neoadjuvant chemotherapy were excluded. Local recurrence-free survival rates were estimated using the Kaplan-Meier method. Associations with local recurrence-free survival were evaluated using log-rank tests and Cox proportional hazards regression models. Results 3,075 patients underwent 3,143 BCS between 1988 and 2001. Mean age at BCS was 61 years (range 21-98). There were 177 (5.6%) patients aged &lt;40, 496 (15.8%) 40-49, 763 (24.3%) 50-59, 803 (25.6%) 60-69, and 904 (28.8%) who were 70+ years old at time of surgery. At last follow-up, 214 patients (6.9%) experienced a local recurrence at a median of 3.4 years following BCS (range 0.1-14.4). Median follow-up for patients who did not experience a local recurrence was 8.7 years (range 0.0-20.2). The 5-year local recurrence-free survival rate was 95.0%. The frequency of local recurrences by age group were as follows: age &lt;40 — 11.9%; age 40-49 — 5.9%; age 50-59 — 5.9%; age 60-69 — 7.6%; age 70 and older — 6.4%. The 5-year local recurrence-free survival rates for these age groups were 90.0%, 95.4%, 95.6%, 95.4%, and 94.7%, respectively (p=0.041; log-rank test). On univariate analysis, patients &lt;40 years old were nearly twice as likely to experience a local recurrence following BCS compared with patients DCIS was associated with an increased risk of local recurrence compared with T1, T2, T3, or T4 disease (HR 2.25; P&lt;0.001). Factors associated with a decreased risk of local recurrence on univariate analysis included ER positivity (HR 0.46; P&lt;0.001), PR positivity (HR 0.60; p=0.001), adjuvant radiation (HR 0.48; p=0.007) and endocrine therapy (HR 0.65; p=0.012). Multivariate analysis of patients with complete data (n=2126) demonstrated that age &lt;40 and node positivity were associated with an increased risk of local recurrence, while ER positivity, adjuvant radiation and endocrine therapy were associated with a decreased risk of local recurrence. Multivariable analysis of local recurrence after BCS Conclusion Risk factors for local recurrence after BCS include young age, node positivity, ER and PR negativity and absence of adjuvant radiation and endocrine therapy. Patients under age 40 are at increased risk of local recurrence following BCS for breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-02.

RhoU is an atypical Rho family member with high homology to CDC42 but containing unique N- and C-terminal extensions. The mechanisms regulating RhoU activation, as well as its downstream effectors, are not fully characterized. We show that after epidermal growth factor (EGF) stimulation RhoU colocalizes with EGF receptor (EGFR) on endosomes, which requires both its N- and C-terminal extension sequences. Moreover, RhoU physically associates with activated EGFR in a GRB2-dependent manner through specific proline-rich motifs within its N-terminus. Mutation of these proline-rich sequences or suppression of GRB2 by RNA interference abrogates the interaction of RhoU with activated EGFR, as well as EGF-stimulated RhoU GTP binding. In addition, RhoU is involved in EGFR-mediated signaling, leading to AP1 transcriptional activity and cell migration in pancreatic cancer cells, events that require its interaction with the Grb2–EGFR complex. Taken together, the data suggest a unique regulatory mechanism by which RhoU interaction with SH3 adaptor proteins might serve to integrate growth factor receptor signaling with RhoU activation.

AbstractMinimally invasive techniques have had a marked impact on colorectal surgery despite the limited adoption of such techniques. Patients stay in the hospital a shorter time, experience less pain, and have less chance of developing a wound infection, an incisional hernia, a bowel obstruction, or difficulty becoming pregnant. Training courses have undergone metamorphosis from ad hoc animate courses to highly defined educational opportunities, and fellowships have had to respond to the educational demands of trainees demanding to be exposed to minimally invasive techniques.