Spitzer Warm Mission Workshop Introduction

The Spitzer Warm Mission Workshop was held June 4–5, 2007, to explore the science drivers for the warm Spitzer mission and help the Spitzer Science Center develop a new science operations philosophy. We must continue to maximize the science return with the reduced resources available, both using (a) the shortest two IRAC channels, and (b) archival research with the rich Spitzer archive. This paper summarizes the overview slides presented to the workshop participant

Biology, Metastatic Patterns, and Treatment of Patients with Triple-Negative Breast Cancer

Of the estimated 1 million cases of breast cancer diagnosed annually worldwide, it is estimated that over 170,000 will harbor the triple-negative (estrogen receptor/progesterone receptor/HER2–negative) phenotype. Most, though not all, triple-negative breast cancers will be basal-like on gene expression micorarrays. The basal-like molecular subtype exhibits a unique molecular profile and set of risk factors, aggressive and early pattern of metastasis, limited treatment options, and poor prognosis. Large population-based studies have identified a higher proportion of triple-negative breast tumors among premenopausal African American women, and a suggestion that increased parity, younger age at first-term pregnancy, shorter duration of breast feeding, and elevated hip-to-waist ratio might be particular risk factors. When BRCA1 mutation carriers develop breast cancer, it is usually basal-like; given the central role of BRCA1 in DNA repair, this could have profound therapeutic implications. When diagnosed, triple-negative breast cancers illustrate preferential relapse in visceral organs, including the central nervous system. Although initial response to chemotherapy might be more profound, relapse is early and common among triple-negative breast cancers compared with luminal breast cancers. The armamentarium of “targeted therapeutics” for triple-negative breast cancer is evolving and includes strategies to inhibit angiogenesis, epidermal growth factor receptor, and other kinases. Finally, the positive association between triple-negative breast cancer and BRCA mutations makes inhibition of poly(adenosine diphosphate-ribose) polymerase–1 an attractive therapeutic strategy that is in active study

Clinical trial update: implications and management of residual disease after neoadjuvant therapy for breast cancer

Neoadjuvant chemotherapy for breast cancer has a well-established role in the management of patients with locally advanced or early stage disease. Multiple trials have demonstrated superior survival outcomes in individuals achieving a pathologic complete response at the time of definitive surgery, and sophisticated genetic methods may predict which patients will be in this category. Those with less than a pathologic complete response remain at significant risk of recurrent disease, and currently no further standard therapy exists. Ongoing studies of novel agents may lead to improved therapeutic outcomes for this high-risk population

The management of early-stage and metastatic triple-negative breast cancer: A review

Triple negative breast cancer (TNBC) defined as lacking expression of the estrogen receptor, progesterone receptor and HER2, comprises approximately 15% of incident breast cancers and is over-represented among those with metastatic disease. It is increasingly clear that TNBC is heterogeneous and that there are several biologically distinct subtypes within TNBC, in particular the basal-like subtype but also the claudin-low, among others. While the incidence of BRCA mutations across all subsets of breast cancer is quite low (~5%), BRCA mutations are more common among those with TNBC (~20%) and may have therapeutic implications. The general principles guiding the use of chemotherapy and radiation therapy do not differ dramatically between early stage TNBC and non-TNBC. There is a trend, however, to treat TNBC at a lower stage with chemotherapy as this is the only way to systemically reduce recurrence risk. In the metastatic setting, while cytotoxic chemotherapy is the mainstay of treatment for advanced TNBC, there are many promising targeted therapies in development in both the preclinical and early phase clinical trial settings. While the treatment of TNBC remains a challenge, coordinated efforts between clinician/scientist partnerships providing a comprehensive understanding of TNBC genomic, proteomic and other biologic processes may result in individualized therapy for TNBC faster than other subtypes -- driven by both the heterogeneity we know exists within this clinical entity and the intense need for improved treatment

Disparities in Use of Human Epidermal Growth Hormone Receptor 2–Targeted Therapy for Early-Stage Breast Cancer

Trastuzumab is a key component of adjuvant therapy for stage I to III human epidermal growth factor receptor 2 (HER2)–positive breast cancer. The rates and patterns of trastuzumab use have never been described in a population-based sample. The recent addition of HER2 information to the SEER-Medicare database offers an opportunity to examine patterns of trastuzumab use and to evaluate possible disparities in receipt of trastuzumab

The Spitzer Warm Mission Science Prospects

After exhaustion of its cryogen, the Spitzer Space telescope will still have a fully functioning two-channel mid-IR camera that will have sensitivities better than any other ground or space-based telescopes until the launch of JWST. This document provides a description of the expected capabilities of Spitzer during its warm mission phase, and provides brief descriptions of several possible very large science programs that could be conducted. This information is intended to serve as input to a wide ranging discussion of the warm mission science, leading up to the Warm Mission Workshop in June 2007

Understanding how breast cancer patients use risk information from genomic tests

We sought to examine how patients’ treatment decisions incorporate potentially conflicting information from standard clinical indicators (e.g., tumor size) and genomic tests for breast cancer recurrence risk

Parental Involvement in Education: A Comparison of English and Spanish Speaking Parents

We examined the educational involvement of English speaking and Spanish speaking parents of students in a Dual Language Program. Parents responded to open-ended questions about how they were involved, what they would like to be involved in but were not, and what barriers prevented them from being more involved. Monitoring/assisting with homework was the most frequently mentioned involvement activity fir both groups, followed by reading with their children, school involvement and communication, and providing social and emotional support to their children. The top areas in which parents wanted to do more were school involvement and communication, social and emotional support, homework assistance/monitoring and parental development. Time and language/educational issues predominated as barriers to parental involvement with the former cited more by English speaking parents and the latter more by Spanish speaking parents

Racial Variation in the Uptake of Onco type DX Testing for Early-Stage Breast Cancer

Oncotype DX (ODX) is a tumor gene-profiling test that aids in adjuvant chemotherapy decision-making. ODX has the potential to improve quality of care; however, if not equally accessible across racial groups, disparities in cancer care quality may persist or worsen. We examined racial disparities in ODX testing uptake

Physical activity, weight, and outcomes in patients receiving chemotherapy for metastatic breast cancer (C40502/Alliance)

Background: Obesity and inactivity are associated with increased risk of cancer-related and overall mortality in breast cancer, but there are few data in metastatic disease. Methods: Cancer and Leukemia Group B 40502 was a randomized trial of first-line taxane-based chemotherapy for patients with metastatic breast cancer. Height and weight were collected at enrollment. After 299 patients enrolled, the study was amended to assess recreational physical activity (PA) at enrollment using the Nurses\u27 Health Study Exercise Questionnaire. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using stratified Cox modeling (strata included hormone receptor status, prior taxane, bevacizumab use, and treatment arm). All statistical tests were 2-sided. Results: A total of 799 patients were enrolled, and at the time of data lock, median follow-up was 60 months. At enrollment, median age was 56.7 years, 73.1% of participants had hormone receptor-positive cancers, 42.6% had obesity, and 47.6% engaged in less than 3 metabolic equivalents of task (MET) hours of PA per week (\u3c1 hour of moderate PA). Neither baseline body mass index nor PA was statistically significantly associated with PFS or OS, although there was a marginally statistically significant increase in PFS (hazard ratio = 0.83, 95% confidence interval = 0.79 to 1.02; Conclusions: In a trial of first-line chemotherapy for metastatic breast cancer, rates of obesity and inactivity were high. There was no statistically significant relationship between body mass index and outcomes. More information is needed regarding the relationship between PA and outcomes