Survivorship care planning, quality of life, and confidence to transition to survivorship: A randomized controlled trial with women ending treatment for breast cancer.

PURPOSE: The Polaris Oncology Survivorship Transition (POST) system is a computer-based program that integrates information from the electronic health record, oncology team, and the patient to produce a personalized Survivorship Care Plan. The purpose of this study was to compare the POST to treatment as usual on confidence, quality of life, and interest in mental health referrals in women ending treatment for breast cancer. SAMPLE: Two hundred women (100 POST, 100 treatment as usual) ending treatment for breast cancer were enrolled in a randomized controlled trial. DESIGN: Women randomized to the POST condition received a personalized care plan during a baseline/intervention appointment. At enrollment and baseline/intervention, a number of outcomes were examined in this study, including confidence to enter survivorship measured by the Confidence in Survivorship Index (CSI) and Quality of Life (QOL). One, three, and six month follow up assessments were also conducted. FINDINGS: Treatment groups did not differ in terms of QOL scores at any time points. Mean CSI scores were statistically different between POST and treatment as usual at baseline for the total CSI score and both subscales, but only for confidence in knowledge about prevention and treatment at the 1-month follow-up. All significant differences were in favor of the POST intervention as mean CSI scores were higher for participants who received the POST intervention as opposed to treatment as usual. These findings disappeared at the 3 and 6 month follow up assessments. Finally, patients who received the POST intervention were twice as likely to request mental health/social services referrals compared to women who received treatment as usual. IMPLICATIONS: Oncologists may use the POST to build personalized care plans for women ending treatment for cancer, which may enhance patients' confidence in the short term as well as encourage use of mental health resources.

Coordination and optimization of FDG PET/CT and COVID-19 vaccination; Lessons learned in the early stages of mass vaccination.

As the world embarks on mass vaccination for COVID-19, we are beginning to encounter unintended dilemmas in imaging oncology patients; particularly with regards to FDG PET/CT. In some cases, vaccine-related lymphadenopathy and FDG uptake on PET/CT can mimic cancer and lead to confounding imaging results. These cases where findings overlap with cancer pose a significant dilemma for diagnostic purposes, follow-up, and management leading to possible treatment delays, unnecessary repeat imaging and sampling, and patient anxiety. These cases can largely be avoided by optimal coordination between vaccination and planned imaging as well as preemptive selection of vaccine administration site. This coordination hinges on patient, oncologist, and radiologists' awareness of this issue and collaboration. Through close communication and patient education, we believe this will eliminate significant challenges for our oncology patients as we strive to end this pandemic.

Teaching of Independent Exercises for Prehabilitation in Breast Cancer.

We attempted to determine the feasibility of studying prehabilitation exercises to improve shoulder pain and abduction range of motion (ROM) after breast cancer surgery. We evaluated methods of exercise teaching and assessed effect on postsurgical seroma formation. This was a feasibility study with two non-blinded groups of subjects randomized by timing of appointment. This single-site study was performed at an academic tertiary medical center. Sixty cancer patients were randomly assigned to either group 1, in-person teaching arm, n = 36, or group 2, video-only teaching arm, n = 24. Forty-five patients completed the study. Shoulder exercises were assigned to both groups 1 month prior to surgery during evaluation. Group 1 received in-person instruction on exercises, plus an information sheet with exercises and a link to an online video. Group 2 received only the information sheet with exercises and a link to the online video. The primary outcomes considered are as follows: exercise compliance, shoulder pain (via visual analog scale), shoulder abduction ROM (via goniometer), and presence or absence of seroma. Seventy-six percent of study patients chose to exercise. There was no difference in exercise compliance between in-person teaching versus video teaching (75 %, 24/32 vs. 77 %, 10/13, OR = 1.03). Sixty-six of patients (20/30) lost greater than 10° shoulder abduction ROM at 1 month post surgery. Twenty-nine of patients (9/31) had worse shoulder pain than baseline at 1 month post surgery (24 %, 6/25 exercisers, and 50 %, 3/6 non-exercisers). Fifteen percent of patients (4/27) had worse shoulder pain than baseline at 3 months post surgery (8 %, 2/23 exercisers, and 100 %, 2/2 non-exercisers). Prehabilitation exercise program inferred no additional risk of seroma formation (Exercisers 21 %, 7/33 vs. non-exercisers 22 %, 2/9, OR = 0.94). Our subjects were able to perform three exercises independently in the preoperative period. A high-quality randomized controlled trial is necessary to assess the appropriate timing and efficacy of this intervention.

Prenatal Maternal Physical Activity and Stem Cells in Umbilical Cord Blood.

PURPOSE: Early life processes, through influence on fetal stem cells, affect postnatal and adult health outcomes. This study examines the effects of physical activity before and during pregnancy on stem cell counts in umbilical cord blood. METHODS: We isolated mononuclear cells from umbilical cord blood samples from 373 singleton full-term pregnancies and quantified hematopoietic (CD34(+), CD34(+)CD38(-), and CD34(+) c-kit(+)), endothelial (CD34(+)CD133(+), CD34(+)CD133(+)VEGFR2(+), CD34(+)VEGFR2(+), and CD133(+)VEGFR2(+)), and putative breast (EpCAM(+), EpCAM(+)CD49f(+), EpCAM(+)CD49f(+)CD117(+), CD49f(+)CD24(+), CD24(+)CD29(+), and CD24(+)CD29(+)CD49f(+)) stem/progenitor cell subpopulations by flow cytometry. Information on physical activities before and during pregnancy was obtained from questionnaires. Weekly energy expenditure was estimated based on metabolic equivalent task values. RESULTS: Prepregnancy vigorous exercise was associated positively with levels of endothelial CD34(+)CD133(+), CD34(+)CD133(+)VEGFR2(+), CD34(+)VEGFR2(+), and CD133(+)VEGFR2(+ )progenitor cell populations (P = 0.02, P = 0.01, P = 0.001, and P = 0.003, respectively); positive associations were observed in samples from the first births and those from the second or later births. Prepregnancy moderate and light exercises and light exercise during the first trimester were not significantly associated with any stem/progenitor cell population. Light exercise during the second trimester was positively associated with CD34(+)VEGFR2(+) endothelial progenitor cells (P = 0.03). In addition, levels of EpCAM(+)CD49f(+) and CD49f(+)CD24(+) breast stem cells were significantly lower among pregnant women who engaged in vigorous/moderate exercise during pregnancy (P = 0.05 and P = 0.02, respectively). CONCLUSIONS: Vigorous exercise before pregnancy increases the number of endothelial progenitor cells in umbilical cord blood and thus could potentially enhance endothelial function and improve cardiovascular fitness in the offspring. Findings of lower levels of putative breast stem cell subpopulations could have implications on exercise and breast cancer prevention. Prenatal effects of exercise on fetal stem cells warrant further studies.

Effect of preeclampsia on umbilical cord blood stem cells in relation to breast cancer susceptibility in the offspring.

Women born from a preeclamptic (PE) pregnancy are associated with a lower risk of breast cancer. Prenatal and early-life exposures are hypothesized to influence breast cancer susceptibility through their effect on stem cells. We examined stem cell populations in umbilical cord blood from PE pregnancies and compared with those from pregnancies without this condition. We isolated mononuclear cells from 58 PE and 197 normotensive (non-PE) umbilical cord blood samples and examined the different stem cell populations. Hematopoietic (CD34(+) and CD34(+)CD38(-)), endothelial (CD34(+)CD133(+), CD34(+)VEGFR2(+), CD133(+)VEGFR2(+) and CD34(+)CD133(+)VEGFR2(+)), and putative breast (EpCAM(+), EpCAM(+)CD49f(+), EpCAM(+)CD49f(+)CD117(+), CD49f(+)CD24(+), CD24(+)CD29(+) and CD24(+)CD29(+)CD49f(+)) stem/progenitor cell subpopulations were quantified by flow cytometry and compared between PE and non-PE samples. Hematopoietic CD34(+) cell counts were significantly lowered in PE compared with non-PE samples (P = 0.039, Kruskal-Wallis test). Levels of CD34(+)CD133(+) endothelial progenitor cells were also lower in PE samples (P = 0.032, multiple regression analysis). EpCAM(+) and EpCAM(+)CD49f(+) putative breast stem cell levels were significantly lowered in PE subjects (multiple regression analysis: P = 0.038 and 0.007, respectively). Stratifying by newborn gender, EpCAM(+) and EpCAM(+)CD49f(+) stem cells were significantly lowered in PE samples of female, but not male, newborns. Umbilical cord blood samples from pregnancies complicated by preeclampsia thus had significantly lower levels of hematopoietic, endothelial, and putative breast stem cells than non-PE controls. With a lowered breast cancer risk for offspring of a PE pregnancy, our findings provide support to the hypothesis that susceptibility to breast oncogenesis may be affected by conditions and processes during the prenatal period.

IMP3 is a novel biomarker for triple negative invasive mammary carcinoma associated with a more aggressive phenotype.

IMP3, an oncofetal protein, is a member of the insulin-like growth factor-II (IGF-II) mRNA-binding protein family. Its relevance as a novel biomarker in lung, pancreatic, renal, and cervical adenocarcinoma was recently revealed. However, its role in breast carcinogenesis and tumor progression is not yet established. Basal-like carcinoma was initially identified by gene expression profiling. It accounts for 15% to 30% of all breast cancers. These tumors express basal epithelial markers including cytokeratin 5 but lack expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), therefore, are often referred to as triple negative breast cancer. They have been found to be associated with a worse overall and disease-free survival. In this retrospective study, we examined the IMP3 expression in invasive ductal carcinoma of the breast and correlated its expression with morphological and biologic prognostic factors. The study group comprised 138 cases of invasive ductal carcinoma retrieved from the surgical pathologic files for a 10-year period from 1997 to 2006. Survival data and clinical stage were available on all 138 patients. Tumor characteristics including size, grade, lymphovascular invasion, necrosis, lymph node metastasis, estrogen receptor, progesterone receptor, and HER2 status were obtained from pathologic reports. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue using mouse monoclonal antibody against IMP3 and CK5/6. Of the 138 breast cancer cases, IMP3 expression was seen in 45 (33%). Twenty-five of the IMP3+ cases were triple negative. We found significant correlation between IMP3 expression and higher grade (P = .001), necrosis (P< .0001) triple negative, and CK5/6 expression (P < .0001 for each). Cox multivariate analysis showed a hazard ratio of IMP3 expression at 3.14 (P = .05). IMP3 is a novel biomarker for triple negative (basal-like) invasive mammary carcinoma, and its expression is associated with a more aggressive phenotype and decreased overall survival.

HER-2 status in breast cancer: correlation of gene amplification by FISH with immunohistochemistry expression using advanced cellular imaging system.

It has become important to accurately evaluate the status of HER-2/neu in invasive breast cancer, especially when one is considering the use of anti-HER-2 monoclonal antibody therapy (Trastuzumab). Almost one third of invasive breast carcinomas overexpress the HER-2/neu protein, so the use of the anti-HER-2/neu monoclonal antibody Herceptin (trastuzumab) to block the protein has become important in the management of and in prolonging the survival for patients with metastatic breast cancer. The effectiveness of this therapy is dependent on accurately evaluating the HER-2 status in these tumors, which can be done either by studying the expression of HER-2 protein by immunohistochemistry (IHC) or by evaluating HER-2 gene amplification by fluorescent in situ hybridization (FISH). Since interobserver variability may occur in manually grading HER-2 protein expression by IHC, the aim of this study was to compare the HER-2/neu expression by IHC using a computer-based image analysis system with that of the gene amplification by FISH. Formalin-fixed paraffin-embedded archival tissue from 108 primary infiltrating ductal carcinomas were immunostained using the HercepTest (DAKO). To reduce interobserver variability, membrane staining was evaluated using the Automated Cellular Imaging System (ACIS) by ChromaVision, and the cases were divided into four groups: group 1 (n=23) with HER-2/neu expression ACIS score less than or equal to 1.5; group 2 (n=17) with a score ranging from 1.6 to 1.9; group 3 (n=46) with a score 2.0 to 2.5; and group 4 (n=22) with a score greater than or equal to 2.6. FISH was performed on all of the 108 cases using the PathVysion HER-2/neu DNA probe kit from Vysis Inc. All cases were also manually reviewed and graded as negative, 1+, 2+, and 3+ according to the DAKO HercepTest grading scheme. Cases with negative and 1+immunostaining were considered as HER-2 not overexpressed, and cases with 2+ and 3+ staining were classified as showing HER-2 overexpression. In group 1, 1 of 23 (4%), in group 2, 2 of 17 (12%), in group 3, 5 of 46 (11%), and in group 4, 19 of 22 (86%) cases showed gene amplification by FISH. Furthermore, in group 4 all 15 (100%) cases with an ACIS score of 3 or greater were FISH positive. Correlation with manual IHC score and FISH showed that 2 of the 23 (9%) IHC negative (0 and 1+) cases and 25 of the 85 (29%) IHC positive (2+ and 3+) cases showed gene amplification by FISH. This study shows that the amplification of the HER-2/neu gene correlates better with overexpression of the HER-2/neu protein by IHC when the score is either less than 1.5 or greater than 2.6 by ACIS. Therefore, FISH may be useful to better evaluate HER-2/neu status in breast cancer in cases where the ACIS score by immunohistochemistry is 1.6 to 2.5, and since the correlation is so good, FISH may not be needed for HER-2 evaluation in cases with ACIS scores less than 1.5 and greater than 2.6.