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Biomedical subjects

Laura Esserman

Publications and source records attributed to Laura Esserman.

16 recordsLinked to original sources
PubMed2006

Evaluation of a visit preparation intervention implemented in two rural, underserved counties of Northern California.

OBJECTIVE: Evaluate satisfaction with visit preparation at three rural resource center sites. METHODS: The resource centers sent eight employees and two volunteers for training at UCSF in Consultation Planning (CP). CP is a service to help patients make a list of questions before seeing their doctors. Researchers used multivariate ordered logistic regression analysis to investigate the variation in satisfaction among 99 CP Clients served by the resource centers in 2003. RESULTS: Sixty-seven CP Clients who completed surveys were highly satisfied (mean=8.67, standard deviation (S.D.)=1.85, range=5-10). Variation in satisfaction was associated only with whether or not the CP Provider was a breast cancer survivor serving a breast patient (p=0.005). Satisfaction was not associated with CP Client demographics; type of upcoming medical visit; or CP Provider age, remuneration status, nursing background, and volume of CP Clients. CONCLUSION: Community-based resource centers have implemented CP to the satisfaction of their clients. Further research should expand the delivery of CP to more underserved members of the community and evaluate its acceptability and impact. There may be a therapeutic alliance formed when survivors provide CP to newly diagnosed patients. PRACTICE IMPLICATIONS: CP should be considered by patient support programs wishing to expand their client services to include visit preparation.

Adult↗
PubMed2005

Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry.

CONTEXT: Ten years after BRCA1 and BRCA2 were first identified as major breast cancer susceptibility genes, the spectrum of mutations and modifiers of risk among many ethnic minorities remain undefined. OBJECTIVES: To characterize the clinical predictors, spectrum, and frequency of BRCA1 and BRCA2 mutations in an ethnically diverse high-risk clinic population and to evaluate the performance of the BRCAPRO statistical model in predicting the likelihood of a mutation. DESIGN, SETTING, AND PARTICIPANTS: Comparative analysis of families (white, Ashkenazi Jewish, African American, Hispanic, Asian) with 2 or more cases of breast and/or ovarian cancer among first- and second-degree relatives. Families were identified at US sites between February 1992 and May 2003; in each family, the individual with the highest probability of being a mutation carrier was tested. MAIN OUTCOME MEASURES: Frequency of BRCA1 and BRCA2 mutations and area under the receiver operating characteristic curve for the BRCAPRO model. RESULTS: The mutation spectrum was vastly different between families of African and European ancestry. Compared with non-Hispanic, non-Jewish whites, African Americans had a lower rate of deleterious BRCA1 and BRCA2 mutations but a higher rate of sequence variations (27.9% vs 46.2% and 44.2% vs 11.5%; P<.001 for overall comparison). Deleterious mutations in BRCA1 and BRCA2 were highest for Ashkenazi Jewish families (69.0%). Early age at diagnosis of breast cancer and number of first- and second-degree relatives with breast and ovarian cancer were significantly associated with an increased likelihood of carrying a BRCA1 or BRCA2 mutation. In discriminating between mutation carriers, BRCAPRO performed as well in African American families as it did in white and Jewish families, with an area under the curve of 0.77 (95% confidence interval, 0.61-0.88) for African American families and 0.70 (95% confidence interval, 0.60-0.79) for white and Jewish families combined. CONCLUSIONS: These data support the use of BRCAPRO and genetic testing for BRCA1 and BRCA2 mutations in the management of high-risk African American families. Irrespective of ancestry, early age at diagnosis and a family history of breast and ovarian cancer are the most powerful predictors of mutation status and should be used to guide clinical decision making.

Adult↗
PubMed2005

The effect of sentinel node tumor burden on non-sentinel node status and recurrence rates in breast cancer.

BACKGROUND: Routine axillary lymph node dissection (ALND) after selective sentinel lymphadenectomy (SSL) in the treatment of breast cancer remains controversial. We sought to determine the need for routine ALND by exploring the relationship between sentinel lymph node (SLN) and non-SLN (NSLN) status. We also report our experience with disease relapse in the era of SSL and attempt to correlate this with SLN tumor burden. METHODS: This was a retrospective study of 390 patients with invasive breast cancer treated at a single institution who underwent successful SSL from November 1997 to November 2002. RESULTS: Of the 390 patients, 115 received both SSL and ALND. The percentage of additional positive NSLNs in the SLN-positive group (34.2%) was significantly higher than in the SLN-negative group (5.1%; P = .0004). The SLN macrometastasis group had a significantly higher rate of positive NSLNs (39.7%) compared with the SLN-negative group (5.1%; P = .0001). Sixteen patients developed recurrences during follow-up, including 6.1% of SLN-positive and 3.3% of SLN-negative patients. Among the SLN macrometastasis group, 8.7% had recurrence, compared with 2.2% of SLN micrometastases over a median follow-up period of 31.1 months. One regional failure developed out of 38 SLN-positive patients who did not undergo ALND. CONCLUSIONS: ALND is recommended for patients with SLN macrometastasis because of a significantly higher incidence of positive NSLNs. Higher recurrence rates are also seen in these patients. However, the role of routine ALND in patients with a low SLN tumor burden remains to be further determined by prospective randomized trials.

Adult↗
PubMed2005

Development of a novel method for measuring in vivo breast epithelial cell proliferation in humans.

Cell proliferation plays an important role in all stages of carcinogenesis. Currently, no safe, direct, in vivo method of measuring breast epithelial cell (BEC) proliferation rates in humans exists. Static immunohistochemical markers of cell proliferation, such as Ki-67 and PCNA indices, have technical limitations including high inter-lab variability, inaccuracy in the presence of agents that cause G1/S cell cycle block and inadequate sensitivity in post-menopausal women with low BEC proliferation rates. We describe here a safe, direct method of measuring BEC proliferation rates in vivo in women using heavy water ((2)H(2)O) labeling coupled with mass spectrometric analysis. Proliferation of normal and tumor BEC was measured from breast tissue biopsies in women undergoing mastectomy (n = 11) and normal BEC from healthy volunteers (n = 16). Women took heavy water (50-150 ml per day) for 1-4 weeks. Pre-menopausal women had significantly higher proliferation rates than post-menopausal women (0.7 +/- 0.1 versus 0.2 +/- 0.1 new cells per day, respectively), and tumor BEC had different proliferation rates than normal BEC from the same breast. The method is analytically reproducible and remains sensitive in the range of low proliferation rates. In summary, this novel method of measuring BEC proliferation in vivo holds promise for assessing the effects of anti-proliferative chemopreventive and chemotherapeutic agents.

Adult↗
PubMed2005

Recruitment, genetic counseling, and BRCA testing for underserved women at a public hospital.

Genetic counseling and testing for heritable susceptibility to breast cancer caused by mutations in BRCA genes are largely unavailable to underserved women in the United States. Starting in 2002 the UCSF Cancer Risk Program offered this service free of charge to poor and medically indigent women at San Francisco General Hospital (SFGH). One recruitment strategy was a single-page questionnaire in four languages administered to women waiting for mammograms at SFGH. This report analyzes our first 3 years of experience with the recruitment questionnaire and compares the patient demographics and BRCA test results at SFGH with a more typical population undergoing genetic counseling and testing at UCSF's Mt. Zion Hospital (MZH). To our knowledge this is the first comprehensive clinical service for hereditary breast cancer in a U.S. public hospital. The ethnic mix of all 350 patients counseled was Caucasian 49% (approximately 20% of Caucasians reported Ashkenazi Jewish ancestry), Latina, 26%; African American, 13%; and Asian/other, 12%. Compared to the MZH population, SFGH patients were more ethnically diverse, less educated and more likely to be unemployed. Of 72 patients tested for BRCA mutations, 51 (71%) were negative, 5 were BRCA1 positive, and 12 were BRCA2 positive. Four (1 Caucasian, 1 Latina, 2 African American) had a total of 13 BRCA variants of unknown significance (VUS). The ratio of BRCA1/BRCA2 positive SFGH patients (5/12) was reversed compared to MZH (119/91). We evaluated 4573 recruitment questionnaires and 280 (6%) were judged to represent a high risk of heritable cancer. After additional screening and referral negotiation, 74 were scheduled for counseling. We judged the recruitment questionnaire to be a feasible, efficient, and reasonably cost-effective way to identify women at high risk of hereditary cancer in a traditionally underserved population. Underserved populations present special challenges for genetic counselors because of large, geographically dispersed families, cultural taboos about cancer diagnoses, and social marginalization. Despite these complexities, the clinical service at SFGH has been well accepted by patients and staff. Our successful venture can serve as a model for other public hospitals contemplating this clinical service.

Adult↗
PubMed2004

Applying the neoadjuvant paradigm to ductal carcinoma in situ.

Local treatment options for ductal carcinoma in situ (DCIS) are virtually identical to those for early invasive breast cancer, despite the fact that the survival from this condition is much higher. Our ability to more appropriately tailor therapy for DCIS is hampered by a lack of understanding of the natural history of DCIS, our limited ability to predict the rate of progression to invasive cancer and the response to therapy, and the absence of tools to follow patients who have not had invasive treatments. Neoadjuvant therapy, which has been proven to be both safe and effective in tailoring treatments for invasive cancer, could be ideally suited to DCIS. However, neoadjuvant therapy requires that doctors and patients delay surgical treatment that has known benefits. In order to successfully introduce this approach into clinical practice, risk assessment and decision support tools will be needed to help physicians and patients feel comfortable that they are not being exposed to unnecessary or excessive risk. In addition, we need better imaging to track extent and progression of disease. Among the possible benefits of the neoadjuvant approach, we may discover that many lesions are responsive and some even reversible, leaving us with treatments that might be tailored to biology and with important clues for breast cancer prevention in high-risk women.

Breast Neoplasms↗
PubMed2004

Neoadjuvant hormonal therapy for ductal carcinoma in situ: trial design and preliminary results.

For some women, the treatment for ductal carcinoma in situ (DCIS) may be even more aggressive than treatments undertaken for early-stage invasive disease. Expectant management is not a tenable alternative, given that in a significant percentage of patients, DCIS eventually progresses to invasive cancer. Nevertheless, if this progression could be halted or reversed with primary medical therapy alone, a significant portion of the 50,000 women diagnosed with DCIS in the United States annually could potentially avoid the morbidity of surgery and radiation for this disease. The most promising therapeutic candidates in this regard are those treatments targeting hormone receptors on breast cancer cells. We have initiated a clinical trial of neoadjuvant hormonal therapy for women with hormone receptor-positive DCIS. We discuss the clinical rationale and study design for this trial and present our preliminary results.

Antineoplastic Agents, Hormonal↗
PubMed2003

An XML message broker framework for exchange and integration of microarray data.

MOTIVATION: Microarrays are an important research tool for the advancement of basic biological sciences. However this technology has yet to be integrated with clinical decision making. We have implemented an information framework based on the Microarray Gene Expression Markup Language (MAGE-ML) specification. We are using this framework to develop a test-bed integrated database application to identify genomic and imaging markers for diagnosis of breast cancer. RESULTS: We developed extensible software architecture for retrieving data from different microarray databases using MAGE-ML and for combining microarray data with breast cancer image analysis and clinical data for correlation studies. The framework we developed will provide the necessary data integration to move microarray research from basic biological sciences to clinical applications. AVAILABILITY: Open source software will be available from SourceForge (http://sourceforge.net/projects/microsoap/).

Database Management Systems↗
PubMed2003

MHC class II enhanceosome: how is the class II transactivator recruited to DNA-bound activators?

MHC class II (MHCII) determinants play a crucial role in the immune response by presenting antigenic peptides to T cells. Their expression is controlled from compact promoters at the transcriptional level. Pre-assembled regulatory factor X (RFX) and nuclear factor Y (NFY) complexes form a platform on DNA. The class II transactivator (CIITA) can then be recruited through multiple protein-protein interactions. In this report, we defined domains of CIITA that are responsible for its interactions with these DNA-bound factors. Furthermore, using DNA-affinity precipitation, we demonstrated that although CIITA binds at least five activators, RFX5, RFXAP, RFXANK/B, NFYB and NFYC, its assembly on the promoter requires the addition of nuclear extracts. We conclude that not only does the platform bind DNA via multiple, spatially constrained nteractions, but that it can recruit only modified and/or complexed CIITA to MHCII promoters.

Amino Acid Sequence↗
PubMed2002

Pretest prediction of BRCA1 or BRCA2 mutation by risk counselors and the computer model BRCAPRO.

BACKGROUND: Because BRCA gene mutation testing is costly, occasionally uninformative, and frequently associated with ethical and legal issues, careful patient selection is required prior to testing. Estimation of BRCA gene mutation probability is an important component of pretest counseling, but the accuracy of these estimates is currently unknown. We measured the performance of eight cancer risk counselors and of a computer model, BRCAPRO, at identifying families likely to carry a BRCA gene mutation. METHODS: Eight cancer risk counselors and the computer model BRCAPRO estimated BRCA gene mutation probabilities for 148 pedigrees selected from an initial sample of 272 pedigrees. The final sample was limited to pedigrees with a proband affected by breast or ovarian cancer and BRCA1 and BRCA2 gene sequencing results unequivocally reported as negative or positive for a deleterious mutation. Sensitivity, specificity, negative predictive value, positive predictive value, and areas under receiver operator characteristics (ROC) curves were calculated for each risk counselor and for BRCAPRO. All statistical tests were two sided. RESULTS: Using a greater-than-10% BRCA gene mutation probability threshold, the median sensitivity for identifying mutation carriers was 94% (range = 81% to 98%) for the eight risk counselors and 92% (range = 91% to 92%) for BRCAPRO. Median specificity at this threshold was 16% (range = 6% to 34%) for the risk counselors and 32% (range = 30% to 34%) for BRCAPRO (P =.04). Median area under the ROC curves was 0.671 for the risk counselors (range = 0.620 to 0.717) and 0.712 (range = 0.706 to 0.720) for BRCAPRO (P =.04). There was a slight, but not statistically significant, improvement in all counselor performance measures when BRCAPRO-assigned gene mutation probability information was included with the pedigrees. CONCLUSIONS: Sensitivity for identifying BRCA gene mutation carriers is similar for experienced risk counselors and the computer model BRCAPRO. Because the computer model consistently demonstrated superior specificity, overall discrimination between BRCA gene mutation carriers and BRCA gene mutation noncarriers was slightly better for BRCAPRO.

Breast Neoplasms↗
PubMed2002

Improving the accuracy of mammography: volume and outcome relationships.

BACKGROUND: Countries with centralized, high-volume mammography screening programs, such as the U.K. and Sweden, emphasize high specificity (low percentage of false positives) and high sensitivity (high percentage of true positives). By contrast, the United States does not have centralized, high-volume screening programs, emphasizes high sensitivity, and has lower average specificity. We investigated whether high sensitivity can be achieved in the context of high specificity and whether the number of mammograms read per radiologist (reader volume) drives both sensitivity and specificity. METHODS: The U.K.'s National Health Service Breast Screening Programme uses the PERFORMS 2 test as a teaching and assessment tool for radiologists. The same 60-film PERFORMS 2 test was given to 194 high-volume U.K. radiologists and to 60 U.S. radiologists, who were assigned to low-, medium-, or high-volume groups on the basis of the number of mammograms read per month. The standard binormal receiver-operating characteristic (ROC) model was fitted to the data of individual readers. Detection accuracy was measured by the sensitivity at specificity = 0.90, and differences among sensitivities were determined by analysis of variance. RESULTS: The average sensitivity at specificity = 0.90 was 0.785 for U.K. radiologists, 0.756 for high-volume U.S. radiologists, 0.702 for medium-volume U.S. radiologists, and 0.648 for low-volume U.S. radiologists. At this specificity, low-volume U.S. radiologists had statistically significantly lower sensitivity than either high-volume U.S. radiologists or U.K. radiologists, and medium-volume U.S. radiologists had statistically significantly lower sensitivity than U.K. radiologists (P<.001, for all comparisons). CONCLUSIONS: Reader volume is an important determinant of mammogram sensitivity and specificity. High sensitivity (high cancer detection rate) can be achieved with high specificity (low false-positive rate) in high-volume centers. This study suggests that there is great potential for optimizing mammography screening.

Breast Neoplasms↗
PubMed1999

Contrast-Enhanced Magnetic Resonance Imaging to Assess Tumor Histopathology and Angiogenesis in Breast Carcinoma.

Contrast-enhanced magnetic resonance imaging (cMRI) is a potentially powerful new tool in the early diagnosis and staging of patients with breast carcinoma. Rapid contrast enhancement is suggestive of carcinoma and likely related to high tumor vascularity. We have developed a new cMRI technique that combines anatomic and kinetic information to help characterize breast carcinomas. Signal enhancement ratio (SER) patterns (which quantitate the kinetics of contrast enhancement using a three time point high-resolution method) were correlated in tumors from 32 patients with histopathology and tumor angiogenesis as measured by intratumoral microvessel density (iMVD). Early signal enhancement with rapid washout of intravenous contrast (i.e., corresponding to high SER values) correlated with high tumor vascularity. We found that TARGET MRI with SER analysis has potential as a tool for characterizing breast carcinoma in vivo. It enables anatomic visualization of tumor and appears to add biologic information as well, such as level of tumor angiogenesis.

Journal Article↗
PubMedDate not supplied

Primary tumor characteristics predict sentinel lymph node macrometastasis in breast cancer.

Selective sentinel lymphadenectomy (SSL) is rapidly becoming the standard of care in the surgical management of patients with early breast cancer. Sentinel lymph node macrometastasis has been well documented in the literature to have a higher risk of nonsentinel node tumor involvement when compared to micrometastasis. The aim of our study was to determine the primary tumor characteristics associated with sentinel node macrometastasis that will allow us to preoperatively determine this subgroup of patients at risk. This study was a retrospective review of 644 patients who underwent successful SSL as part of their surgical treatment of breast cancer at the University of California San Francisco Carol Franc Buck Breast Care Center from November 1997 to August 2003. All patients underwent preoperative lymphoscintigraphy followed by wide excision or mastectomy and sentinel lymphadenectomy with or without axillary lymph node dissection. One hundred twenty-two patients had positive sentinel nodes on histology. Micrometastasis was present in 43 of these patients and macrometastasis in the remaining 79. Statistical analysis showed that a tumor size greater than 15 mm, poor tubule formation by the tumor cells, and lymphovascular invasion were significantly associated with sentinel node macrometastasis. A high mitotic count showed a trend but was not significant in our study. Patients with a tumor size greater than 15 mm, poor tubule formation, and lymphovascular invasion are at risk of having sentinel node macrometastasis. These patients can be identified preoperatively based on imaging and biopsy criteria, allowing the option of selective intraoperative pathologic evaluation of the sentinel node and immediate completion axillary dissection as necessary.

Adult↗
PubMedDate not supplied

Ratio of positive to total number of sentinel nodes predicts nonsentinel node status in breast cancer patients.

Selective sentinel lymphadenectomy (SSL) has replaced axillary lymph node dissection (ALND) for many patients with early breast cancer and negative sentinel lymph nodes (SLNs). Yet many patients with a positive SLN are undergoing unnecessary ALND, as no further disease is found in the axilla. The aim of our study was to determine factors associated with additional positive lymph nodes in the axilla in patients who have a positive SLN. This was a retrospective study of patients undergoing SSL with ALND as part of their treatment for breast cancer at a single institution from November 1997 to August 2003. Only patients with one or more positive SLNs were selected for this study. There were 86 patients who fit our study criteria. Of these, 38% had further positive lymph nodes upon ALND. More than one positive SLN and a ratio of positive SLNs to total SLNs of greater than 0.5 were found to be predictors for additional axillary nodal involvement in both univariate and multivariate analyses. The number of positive SLNs and the ratio of positive SLNs to total SLNs is an indication of total tumor burden in the sentinel nodes and may be a reflection of the propensity of the tumor for further lymphatic invasion in the axillary basin.

Adult↗