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"Lawrence, Julia A."
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Leveraging the past to prepare for the future of Air Force intelligence analysis
\"This report describes steps the U.S. Air Force can take to help ensure that it has the capability needed to provide intelligence analysis support to a broad range of service and combatant commander needs, including support to ongoing irregular warfare operations, and to conventional warfare with a near-peer competitor. It describes lessons from past operations that have direct implications for Air Force intelligence analysis or that Air Force intelligence analysis could help to address. It also describes future challenges for Air Force intelligence analysis. It makes recommendations related to doctrine, training and career field development, analysis tools, and processes that can help to address the lessons from the past and prepare Air Force intelligence analysts for the challenges of the future\"--Publisher's description.
Book
Preferences for breast cancer survivorship care by rural/urban residence and age at diagnosis
Purpose
Preferences for survivorship care among recently treated breast cancer survivors may vary by rural-urban residence and age, but potential differences have not been examined.
Methods
We conducted a cross-sectional survey of survivorship preferences among women treated for non-metastatic breast cancer 6–24 months prior to recruitment.
Results
We surveyed 203 women (66% response) with American Joint Committee on Cancer Stage I or II breast cancer. Rural residents comprised 36.5% of respondents (82.7% White, non-Hispanic; 52.5% < college education) and 29.6% were ≥ 65 years. More than 95% indicated that checking for recurrence, receiving additional treatment, evaluation of side effects, and identification of late effects were “very important” reasons for follow-up care. The most common topics identified as “very important” for survivorship care discussions were recommendations for healthy behaviors (65.3%), best sources for breast cancer information (65.3%), and effects on family (53.3%) and job (53.8%). Women 65 years and older preferred to discuss follow-up care at the time of diagnosis (
p
= 0.002), with younger women preferring during (32%) or after treatment (39.1%). Rural survivors were significantly more likely to identify follow-up care reasons not related to the initial breast cancer as “very important” than urban survivors, including screening for other cancers, and examinations or tests for non-cancer diseases (both
p
= 0.01).
Conclusions
Survivorship care in accordance with national recommendations will likely be accepted by breast cancer survivors. Tailoring breast cancer survivorship care by timing, integration of primary care services, and specific psychosocial topics may best meet the needs of different ages and demographics.
Journal Article
Disparities in barriers to follow-up care between African American and White breast cancer survivors
Purpose
Despite recommendations for breast cancer survivorship care, African American women are less likely to receive appropriate follow-up care, which is concerning due to their higher mortality rates. This study describes differences in barriers to follow-up care between African American and White breast cancer survivors.
Methods
We conducted a mailed survey of women treated for non-metastatic breast cancer in 2009–2011, 6–24 months post-treatment (
N
= 203). Survivors were asked about 14 potential barriers to follow-up care. We used logistic regression to explore associations between barriers and race, adjusting for covariates.
Results
Our participants included 31 African American and 160 White survivors. At least one barrier to follow-up care was reported by 62 %. Compared to White survivors, African Americans were more likely to identify barriers related to out-of-pocket costs (28 vs. 51.6 %,
p
= 0.01), other health care costs (21.3 vs. 45.2 %,
p
= 0.01), anxiety/worry (29.4 vs. 51.6 %,
p
= 0.02), and transportation (4.4 vs. 16.1 %,
p
= 0.03). After adjustment for covariates, African Americans were three times as likely to report at least one barrier to care (odds ratio (OR) = 3.3, 95 % confidence interval (CI) = 1.1–10.1).
Conclusions
Barriers to care are common among breast cancer survivors, especially African American women. Financial barriers to care may prevent minority and underserved survivors from accessing follow-up care. Enhancing insurance coverage or addressing out-of-pocket costs may help address financial barriers to follow-up care among breast cancer survivors. Psychosocial care aimed at reducing fear of recurrence may also be important to improve access among African American breast cancer survivors.
Journal Article
Breast cancer subtype affects patterns of failure of brain metastases after treatment with stereotactic radiosurgery
We investigate the variance in patterns of failure after Gamma Knife™ radiosurgery (GKRS) for patients with brain metastases based on the subtype of the primary breast cancer. Between 2000 and 2010, 154 breast cancer patients were treated with GKRS for brain metastases. Tumor subtypes were approximated based on hormone receptor (HR) and HER2 status of the primary cancer: Luminal A/B (HR+/HER2(−)); HER2 (HER2+/HR(−)); Luminal HER2 (HR+/HER2+), Basal (HR(−)/HER2(−)), and then based on HER2 status alone. The median follow-up period was 54 months. Kaplan–Meier method was used to estimate survival times. Multivariable analysis was performed using Cox regression models. Median number of lesions treated was two (range 1–15) with a median dose of 20 Gy (range 9–24 Gy). Median overall survival (OS) was 7, 9, 11 and 22 months for Basal, Luminal A/B, HER2, and Luminal HER2, respectively (
p
= 0.001), and was 17 and 8 months for HER2+ and HER(−) patients, respectively (
p
< 0.001). Breast cancer subtype did not predict time to local failure (
p
= 0.554), but did predict distant brain failure rate (76, 47, 47, 36 % at 1 year for Basal, Luminal A/B, HER2, and Luminal HER2 respectively,
p
< 0.001). An increased proportion of HER2+ patients experienced neurologic death (46 vs 31 %,
p
= 0.066). Multivariate analysis revealed that HER2+ patients (
p
= 0.007) independently predicted for improved survival. Women with basal subtype have high rates of distant brain failure and worsened survival. Our data suggest that differences in biologic behavior of brain metastasis occur across breast cancer subtypes.
Journal Article
A retrospective review of the metabolic syndrome in women diagnosed with breast cancer and correlation with estrogen receptor
Women diagnosed with obesity and breast cancer have an increased risk of recurrence and death (Protani et al., Breast Cancer Res Treat 123:627–635,
1
). Obesity is associated with the metabolic syndrome—a pathophysiologically distinct inflammatory process comprised of central obesity, insulin resistance, hypertension, and atherogenic dyslipidemia. The relationship of obesity as a risk factor for breast cancer is complex with a protective effect for younger women in contrast to a risk for older women (Kabat et al., Cancer Epidemiol Biomarkers Prev 18:2046–2053,
2
; Ursin et al., Epidemiology 6:137–141,
3
). The metabolic syndrome has been associated with the risk of cancer, and pro-inflammatory circulating factors may be associated with risk of more aggressive breast cancer (Capasso et al., Cancer Biol Ther 10:1240–1243,
4
; Healy et al., Clin Oncol (R Coll Radiol) 22:281–288,
5
; Laukkanen et al., Cancer Epidemiol Biomarkers Prev 13:1646–1650,
6
). We conducted a retrospective review of 860 breast cancer patients to determine the relationship between estrogen receptor status and the metabolic syndrome. We collected the relevant metabolic diagnoses, medications, physical findings, and laboratory values and adapted the National Cholesterol Education Program criteria to define the metabolic syndrome retrospectively. No relationship was found between estrogen receptor status and the individual components of the metabolic syndrome. Based on findings in the medical records, 15% of the women with breast cancer had the metabolic syndrome, and 26% of the women were considered obese, 16% hyperglycemic, 54% hypertensive, and 30% dyslipidemic. The metabolic syndrome was associated with advanced age and African-American race (
P
< 0.001). When adjusted for age, race, and stage, the metabolic syndrome was marginally associated with estrogen receptor-positive tumors (
P
= 0.054). Our findings do not support the concern that the metabolic syndrome may contribute to more biologically aggressive breast cancer.
Journal Article
Current Therapeutic Options for Breast Cancer Central Nervous System Metastases
Opinion statement
Breast cancer metastases to the central nervous system (CNS) has devastating consequences for the individual. As treatment options for metastatic breast cancer expand and as quality of life and overall survival improve, researchers are targeting potential treatments for this sanctuary site. Attention is now being focused on defining the phenotype of breast cancer that has a propensity to metastasize to the CNS. Specific therapies that penetrate the blood brain barrier as well as adjuvant therapies that decrease recurrence in the CNS are currently being investigated. We will review current approaches to the diagnosis, evaluation, and treatment of CNS metastases in breast cancer patients.
Journal Article
Overexpression of cyclin D mRNA distinguishes invasive and in situ breast carcinomas from non-malignant lesions
The elucidation of molecular alterations that occur during human breast cancer progression may contribute to the development of preventative strategies. Using
in situ
hybridizations on a cohort of 94 biopsy lesions, quantitatively increased cyclin D mRNA expression levels were observed in only 18% of benign lesions, which confer no or slightly increased breast cancer risk, and 18% of premalignant atypical ductal hyperplasias, which confer a four to fivefold increase in breast cancer risk. The transition to carcinoma was accompanied by frequent cyclin D mRNA overexpression in 76% of low-grade ductal carcinomas
in situ
, 87% of higher grade comedo ductal carcinomas
in situ
and 83% of infiltrating ductal breast carcinomas. The data identify a molecular event that may separate benign and premalignant human breast lesions from any form of breast carcinoma.
Journal Article
Identification of compounds with preferential inhibitory activity against low-Nm23-expressing human breast carcinoma and melanoma cell lines
We have used the COMPARE computer algorithm and Nm23 expression as a marker of tumor metastatic potential to examine the
in vitro
antiproliferative activity of chemotherapeutic drugs on human breast carcinoma and melanoma cell lines. None of 171 compounds in clinical use or under development and only 40 of 30,000 repository compounds exhibited preferential growth inhibition of low-Nm23-expressing, metastatically aggressive cell lines with a Pearson correlation coefficient of ≤0.64. Characterization of one compound, NSC 645306, is presented including
in vivo
activity in a hollow fiber assay. The data demonstrate a novel approach to drug identification for aggressive human tumors.
Journal Article
Biomarkers as surrogates for cancer development
Biomarkers are routinely applied in the management of chronic diseases to reduce morbidity and mortality through early diagnosis, as well as to assess the necessity for, and responsiveness to, applied interventions. Biomarkers yield mechanistic insights into layers of biologic organization from molecule to organelle, to cell, and finally to cellular organization and tissue. A step-wise approach to the development of tissue-based biomarkers is presented. These biomarkers may serve as molecular targets for scientific inquiry and intervention, as well as approvable endpoints for clinical trials.
Journal Article