Gilchrist L. Jackson

Participation in breast screening programs : a review

Despite recommendations by the American Cancer Society and other organizations for use of screening mammography, data on reported utilization of this procedure by American women show that these guidelines are not being met. We reviewed published studies that reported participation rates or that examined factors associated with participation in selected breast screening programs. In general, women at high risk due to age and family or personal history of breast disease were not more likely to participate in breast screening programs than women without those risk factors. The one group of variables that was fairly consistently associated with participation was the practice of other preventive health behaviors. Women who expressed more concern about their health and who were more knowledgeable about breast cancer screening and its benefits also were more likely to complete mammography. Approaches to increasing participation are discussed in the context of the literature on this subject.

Breast cancer screening behaviors and attitudes in three racial/ethnic groups.

Data from a multiethnic sample of women participating in the American Cancer Society 1987 Texas Breast Screening Project was used to compare attitudes and behaviors related to breast cancer screening for whites, blacks, and Hispanics. In general, similar patterns of association were observed across racial/ethnic groups between a number of demographic and risk factors and prior mammography and recent clinical breast examination (CBE), although the magnitude of the associations varied somewhat across groups. Reasons for not having had prior mammography also were similar across groups, with lack of physician referral and cost cited as the two most important reasons. However, Hispanics were less likely than blacks or whites to report prior breast cancer screening, including mammography, CBE, and breast self‐examination (BSE). This study demonstrated that women of different racial/ethnic backgrounds can be successfully recruited to participate in a patient‐initiated, community‐based program. However, this programmatic approach requires augmentation with other intervention strategies designed to reach low‐income women because women with more years of education and higher family income were overrepresented in all three groups.

Obesity, non‐protein‐bound estradiol levels, and distribution of estradiol in the sera of breast cancer patients

This study attempted to determine the relationship of nutritional status, menopausal status, presence of breast cancer, stage of disease, and tumor estrogen receptor levels to percent non‐protein‐bound estradiol (%NPBE) and percent distribution of estradiol on sex hormone‐binding globulin (SHBG) and albumin in breast cancer patients and control patients. Normal‐weight controls had significantly lower %NPBE compared with overweight controls and normal‐weight and overweight breast cancer patients. There was a significant shift in the percent distribution of estradiol from SHBG to albumin in breast cancer patients, independent of body weight. Elevated %NPBE and abnormal percent estradiol distribution on albumin persisted after mastectomy and were unrelated to menopausal status, presence and stage of disease, and tumor estrogen receptor levels. These results show that breast cancer patients have increased exposure to unbound circulating estradiol and an increased percentage of estradiol bound to albumin, which may influence the availability of estradiol, considering its low binding affinity to albumin. Because these abnormalities persist after mastectomy, the current results may be important in developing dietary intervention protocols that correct %NPBE and abnormal estradiol distribution on binding proteins.

Development of a Prognostic Genetic Signature to Predict the Metastatic Risk Associated with Cutaneous Melanoma

Purpose: The development of a genetic signature for the identification of high-risk cutaneous melanoma tumors would provide a valuable prognostic tool with value for stage I and II patients who represent a remarkably heterogeneous group with a 3% to 55% chance of disease progression and death 5 years from diagnosis. Experimental Design: A prognostic 28-gene signature was identified by analysis of microarray expression data. Primary cutaneous melanoma tumor tissue was evaluated by RT-PCR for expression of the signature, and radial basis machine (RBM) modeling was performed to predict risk of metastasis. Results: RBM analysis of cutaneous melanoma tumor gene expression reports low risk (class 1) or high risk (class 2) of metastasis. Metastatic risk was predicted with high accuracy in development (ROC = 0.93) and validation (ROC = 0.91) cohorts of primary cutaneous melanoma tumor tissue. Kaplan–Meier analysis indicated that the 5-year disease-free survival (DFS) rates in the development set were 100% and 38% for predicted classes 1 and 2 cases, respectively (P < 0.0001). DFS rates for the validation set were 97% and 31% for predicted classes 1 and 2 cases, respectively (P < 0.0001). Gene expression profile (GEP), American Joint Committee on Cancer stage, Breslow thickness, ulceration, and age were independent predictors of metastatic risk according to Cox regression analysis. Conclusions: The GEP signature accurately predicts metastasis risk in a multicenter cohort of primary cutaneous melanoma tumors. Preliminary Cox regression analysis indicates that the signature is an independent predictor of metastasis risk in the cohort presented. Clin Cancer Res; 21(1); 175–83. ©2015 AACR.

Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy.

BACKGROUND A gene expression profile (GEP) test able to accurately identify risk of metastasis for patients with cutaneous melanoma has been clinically validated. OBJECTIVE We aimed for assessment of the prognostic accuracy of GEP and sentinel lymph node biopsy (SLNB) tests, independently and in combination, in a multicenter cohort of 217 patients. METHODS Reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the expression of 31 genes from primary melanoma tumors, and SLNB outcome was determined from clinical data. Prognostic accuracy of each test was determined using Kaplan-Meier and Cox regression analysis of disease-free, distant metastasis-free, and overall survivals. RESULTS GEP outcome was a more significant and better predictor of each end point in univariate and multivariate regression analysis, compared with SLNB (P < .0001 for all). In combination with SLNB, GEP improved prognostication. For patients with a GEP high-risk outcome and a negative SLNB result, Kaplan-Meier 5-year disease-free, distant metastasis-free, and overall survivals were 35%, 49%, and 54%, respectively. LIMITATIONS Within the SLNB-negative cohort of patients, overall risk of metastatic events was higher (∼30%) than commonly found in the general population of patients with melanoma. CONCLUSIONS In this study cohort, GEP was an objective tool that accurately predicted metastatic risk in SLNB-eligible patients.

Comparison of participants and nonparticipants in a work site cancer awareness and screening program

In 1985, Pennzoil Company offered a company-paid cancer awareness and screening program focusing on breast and colorectal cancers for its employees. Following a lecture/slide presentation, employees filled out a risk assessment questionnaire. Those at risk for breast and/or colorectal cancers were invited for consultation, mammography, and/or short colonoscopy. Overall completion rates were 49% for mammography, 20% for the fecal occult blood test, and 31% for short colon oscopy, but these rates varied by risk status. Moreover, the same demographic and risk factors were not consistently associated with completion of the same screening procedure across risk groups. Based on these findings, we suggest that different interventions may need to be developed depending on the risk characteristics of subgroups within the target population.

A survey of physician beliefs and self-reported practices concerning screening for early detection of cancer

Cancer is the second leading cause of death in the United States. Early detection of cancer greatly improves 5-year survival for many sites, and in 1980 the American Cancer Society (ACS) published recommendations for performing cancer screening with the goal of promoting early cancer detection in asymptomatic persons. This cross-sectional survey examined beliefs and practices related to six cancer screening tests and procedures in a group of 68 primary care physicians in a multi-specialty group practice in Houston, Texas. Constructs from the Health Belief Model and Social Cognitive Theory were used to identify factors that might influence performance of cancer screening. Physicians in this study reported greater compliance with ACS recommendations for performance than has been found in other studies, and there is an indication that some screening tests may be performed even when not indicated based on age-specific criteria. Respondents reported performing digital rectal examination, stool occult blood testing, and sigmoidoscopy more frequently in men than in women. No belief factor emerged as being associated with performance of all screening procedures, and associations that were noted for some procedures were not consistent across patient age and gender groups. Some possible directions for further research and development of programs to promote the appropriate and cost effective use of cancer screening are physician education to include information about age and gender appropriate guidelines for screening and opportunities for skills training and practice workshops for some procedures.

Dramatic response from neoadjuvant, spatially fractionated GRID radiotherapy (SFGRT) for large, high-grade extremity sarcoma

Extremity sarcomas are managed surgically with the goal of limb preservation. In order to reduce local recurrence rates, radiation treatment has been used in either the preoperative or postoperative setting for select cases [1]. This combination has proven beneficial for large, high-grade, deeply invasive, or incompletely resected tumors [2]. Due to lower long-term complications rates, neoadjuvant treatment has become favored in cases where predicted postsurgical risks are low [3]. However, high-grade sarcomas rarely completely regress after preoperative radiation [4, 5]. In addition, the median pathological treatment response for high-grade tumors is only 50 %, and patients with pathological necrosis rates less than 95 % are 2.5 times more likely to develop a local recurrence [5, 6]. Thus, very large (>8 cm) sarcomas represent an even greater clinical challenge. This has prompted the addition of chemotherapy to preoperative radiation in the hopes of improving tumor response [6–8] and to evaluate effectiveness of the drugs. Although neoadjuvant chemoradiation shows greater tumor necrosis, it comes at a significant cost. One study showed a 90% risk of grades 3–4 hematologic toxicity with chemoradiation, and a multi-institutional phase II study reported increased hospitalizations and death [7, 8]. Methods