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Biomedical subjects

Joseph P Crowe

Publications and source records attributed to Joseph P Crowe.

At least 19 recordsLinked to original sources
PubMed2006

Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.

Adult↗
PubMed2006

The 2003 revised TNM staging system for breast cancer: results of stage re-classification on survival and future comparisons among stage groups.

BACKGROUND: Changes to TNM staging criteria for breast cancer, introduced in 2003, have resulted in stage re-classification for some tumors. The most frequently implemented change has resulted in tumors associated with more than three positive axillary nodes being upstaged. We hypothesize these TNM staging changes would result in more TNM Stage IIB, IIIA, and IIIB tumors and that disease-specific survival estimates would change under the new staging system. METHODS: A review of data was completed for patients diagnosed with breast cancer between 1 January 1995 and 31 December 2000. Tumors that would have been staged differently under the 2003 system were identified and re-classified. Clinical outcomes were determined and disease-specific survival estimates were compared relative to TNM Stage using the old and new staging systems. Data were analyzed using the log-rank test and the method of Kaplan and Meier was used to generate survival curves. RESULTS: Data were available for 2492 tumors, of which 919 were candidates for re-classification, including 829 old Stage II, 59 old Stage III, and 31 old Stage IV. Of these 919, 159 (17%) underwent stage re-classification using the new system. Separate survival estimates for patients who had been under old stage IIA/B, IIIA/B were generated; patients upstaged from IIA or IIB demonstrated a significant difference in survival. CONCLUSIONS: Stage specific survival curves indicated decreased survival for patients whose tumors had been upstaged from IIA or IIB under the old system; survival for all other patients remained unchanged.

Adult↗
PubMed2006

A data model to predict HER2 status in breast cancer based on the clinical and pathologic profiles of a large patient population at a single institution.

Recently published clinical trial data have produced compelling evidence for increased survival when Herceptin is administered to patients whose tumors are HER2 amplified. Therefore, the accuracy of HER2 status is essential to determine which patients should or should not receive Herceptin. Although HER2 results obtained by FISH and IHC are often in agreement, there is a persistent group of cases in which results are discordant, particularly among tumors with intermediate results. A multivariable analysis was undertaken to determine relative significance of various clinical and pathologic findings for patients diagnosed with infiltrating ductal carcinoma, and a data model was produced that predicts which patients are most likely to have HER2 amplified tumors. Correlates of HER2 amplification were higher Scarff-Bloom-Richardson grade, younger age at diagnosis, and a comedo ductal carcinoma in situ component.

Adult↗
PubMed2006

Prognostic significance of residual breast disease and axillary node involvement for patients who had primary induction chemotherapy for advanced breast cancer.

BACKGROUND: We performed this study to determine the prognostic significance of clinical tumor size, pathologic measurement of residual tumor, and number of positive axillary nodes in the surgical specimen relative to overall survival for patients who underwent primary induction chemotherapy for advanced breast cancer. METHODS: Data, collected prospectively between 1997 and 2002, included clinical tumor-node-metastasis stage, age at diagnosis, hormone receptor status, type of preoperative chemotherapy, histological type, surgical procedure, pathologic measurement in centimeters of residual breast tumor, and the number of positive axillary nodes in the surgical specimen. Univariable correlates of residual breast disease were assessed by using the chi2 test. Recursive partitioning analysis was used to determine the prognostic significance of clinical tumor size, residual tumor size, and pathologic node involvement relative to overall survival. Survival was estimated by using the method of Kaplan and Meier and compared by using the log-rank test. A P value of <.05 was considered significant. RESULTS: Data were available for 85 patients with advanced breast cancer. Although univariable analysis identified increasing age, clinically involved axillary nodes, and a higher clinical tumor-node-metastasis stage as predictors of an increased risk of residual disease, recursive partitioning analysis identified more than three involved axillary nodes in the surgical specimen, with or without any measurable residual breast disease, as the most significant predictor of decreased survival (P<.001). CONCLUSIONS: Pathologic axillary node involvement was the most significant predictor of decreased survival for patients who had undergone primary induction chemotherapy for advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status.

PURPOSE: The extent to which socioeconomic disadvantages and inadequate health care access account for the disproportionately elevated mortality hazard observed in African American compared with white American patients with breast cancer is poorly defined. METHODS: We identified 20 studies reported between January 1980 and June 2005 that provided survival analyses in patients with breast cancer after adjusting for ethnicity and some measurement of socioeconomic status. These studies also adjusted for age and stage of disease at time of diagnosis. RESULTS: The pooled outcome data yielded estimates for the mortality hazard in 14,013 African American and 76,111 white American patients with breast cancer. Studies varied in their methods for assigning socioeconomic status, with most relying on area-wide measures such as census tract and census block data. The combined analysis (adjusted for age, stage, and socioeconomic status) revealed that African American ethnicity was associated with a statistically significant excess mortality risk in overall survival (mortality hazard, 1.27; 95% CI, 1.18 to 1.38) and in breast cancer-specific survival (mortality hazard, 1.19; 95% CI, 1.10 to 1.29). CONCLUSION: Our pooled analysis demonstrated that African American ethnicity is a significant and independent predictor of poor outcome from breast cancer, even after accounting for socioeconomic status by conventional measures. These findings support the need for further investigation of the biologic, genetic, and sociocultural factors that may influence survival in African American patients with breast cancer.

Black People↗
PubMed2006

In vivo margin assessment during partial mastectomy breast surgery using raman spectroscopy.

We present the first demonstration of in vivo collection of Raman spectra of breast tissue. Raman spectroscopy, which analyzes molecular vibrations, is a promising new technique for the diagnosis of breast cancer. We have collected 31 Raman spectra from nine patients undergoing partial mastectomy procedures to show the feasibility of in vivo Raman spectroscopy for intraoperative margin assessment. The data was fit with an established model, resulting in spectral-based tissue characterization in only 1 second. Application of our previously developed diagnostic algorithm resulted in perfect sensitivity and specificity for distinguishing cancerous from normal and benign tissues in our small data set. Significantly, we have detected a grossly invisible cancer that, upon pathologic review, required the patient to undergo a second surgical procedure. Had Raman spectroscopy been used in a real-time fashion to guide tissue excision during the procedure, the additional reexcision surgery might have been avoided. These preliminary findings suggest that Raman spectroscopy has the potential to lessen the need for reexcision surgeries resulting from positive margins and thereby reduce the recurrence rate of breast cancer following partial mastectomy surgeries.

Breast Neoplasms↗
PubMed2006

The clinical applications of mammary ductoscopy.

BACKGROUND: Mammary ductoscopy (MD) is a newly developed endoscopic technique that allows direct visualization and biopsy examination of the mammary ductal epithelium where most cancers originate. The procedure can be performed under local anesthesia in the office setting. This article reviews the rationale, current clinical applications, and limitations of MD. METHODS: A literature search was performed using Pubmed for indexed articles published over the past 30 years using the key words "mammary ductoscopy," "breast ductoscopy," "ductal lavage," and "nipple aspiration." The most important articles were analyzed and discussed. RESULTS: MD is a useful diagnostic adjunct in patients with pathologic nipple discharge. Furthermore, it can reduce the number and extent of duct excision surgeries for pathologic nipple discharge. There is a clear need to design prospective clinical trials that evaluate the potential role of MD in breast cancer screening, guiding risk-reducing strategies, and as an adjunct to breast-conservation surgery. CONCLUSIONS: MD is useful in the management of PND, but its potential role in the early detection or management of breast cancer requires further investigation.

Breast Neoplasms↗
PubMed2006

Identification of breast cancer in patients with pathologic nipple discharge: does ductoscopy predict malignancy?

OBJECTIVE: The purpose of the current study was to review characteristics of patients with nipple discharge who underwent ductoscopy-assisted excisional biopsy who had a final diagnosis of carcinoma. METHODS: A retrospective review was performed of patients presenting with pathologic nipple discharge (PND) who underwent ductoscopy-assisted excisional biopsy and had a final diagnosis of carcinoma. RESULTS: A total of 14 (7%) of 188 patients who underwent ductoscopy-assisted excision had a final pathology of ductal carcinoma-in-situ (DCIS) (12/14, 86%) or invasive breast cancer with DCIS (2/14, 14%). Duct wall irregularities or intraluminal growths were visualized during ductoscopy in 8 of the 14 (57%) breast cancer patients. There were no visual abnormalities noted during ductoscopy that accurately predicted a final diagnosis of malignancy. CONCLUSIONS: Although occult malignancies can be identified in patients undergoing ductoscopy-assisted biopsy for PND, no clear morphologic changes visualized during ductoscopy definitively indicated the presence of malignancy.

Adenocarcinoma↗
PubMed2006

Breast surgery: minimally invasive diagnosis and treatment.

The increasingly large proportion of elderly women in the United States population carries a disproportionate burden of breast cancer. The advent of minimally invasive surgical techniques applicable to breast disease has brought new opportunities to diagnose and treat breast cancer in the older population. This article reviews issues important to the evolving field of breast cancer management in older women: cancer risk and screening considerations, diagnosis and biopsy approaches, and surgical treatment options based on current studies and recommendations.

Aged↗
PubMed2006

Breast cancers with brain metastases are more likely to be estrogen receptor negative, express the basal cytokeratin CK5/6, and overexpress HER2 or EGFR.

Brain metastases (BM) from breast cancer are associated with significant morbidity and mortality. In the current study, we have examined a cohort of breast cancer patients who went on to develop BM for clinical-pathologic features and predictive markers that identify this high-risk subgroup of patients at the time of diagnosis. The primary tumors from 55 patients who developed BM were used to construct a tissue microarray. The clinical and pathologic features were recorded and the tissue microarray was stained for estrogen receptor, human epidermal growth factor receptor 2, cytokeratin 5/6, and epidermal growth factor receptor by immunohistochemistry. This cohort of patients was compared against a group of 254 patients who remain free of metastases (67 mo mean follow-up), and another cohort of 40 patients who developed mixed visceral and bone metastatic disease without brain recurrence over a similar period of time. Breast cancer patients who went on to develop BM were more likely to be <50 years old (P<0.001), and the primary tumors were more likely to be estrogen receptor negative (P<0.001) and high grade (P=0.002). The primary tumors were also more likely to express cytokeratin 5/6 (P<0.001) and epidermal growth factor receptor (P=0.001), and to overexpress human epidermal growth factor receptor 2 (P=0.001). The data presented above suggest a profile for breast cancer patients at increased risk for developing BM. Predictive factors to help identify patients with metastatic breast cancer who are at an increased risk for developing central nervous system recurrence might allow for screening of this population for early detection and treatment or for the development of targeted strategies for prevention.

Brain Neoplasms↗
PubMed2005

The incidence of topoisomerase II-alpha genomic alterations in adenocarcinoma of the breast and their relationship to human epidermal growth factor receptor-2 gene amplification: a fluorescence in situ hybridization study.

Clinical and in vitro evidence supports the concept that human epidermal growth factor receptor-2 ( HER2 ) gene amplification prediction of response to anthracycline-based chemotherapy in breast cancer is not a direct effect of HER2 overexpression, but the result of coamplification of topoisomerase II-alpha ( TOP2A ). We investigated the relationship of TOP2A to HER2 genomic alterations by fluorescence in situ hybridization (FISH) and the correlations with polysomic states for chromosome 17 (CEP17). One hundred thirty-eight cases of breast cancer HER2 gene amplified by 2-color FISH ( HER2 /CEP17) were reevaluated with a 3-color probe set ( HER2 /CEP17/ TOP2A ) to investigate the frequency of coamplification and deletion of TOP2A . TOP2A was never amplified in the absence of HER2 amplification and was coamplified with HER2 in 68 (50%) of 137 cases; HER2 gene copy number was higher than the TOP2A copy number ( P < .01). Of the 137 cases with HER2 amplification, 23 (16%) showed a monoallelic deletion of TOP2A . Of the 43 cases not amplified for HER2 , 27 (63%) were CEP17 eusomic, 13 (30%) polysomic, and 3 (7%) monosomic. Of the HER2 nonamplified cases, 2 (5%) showed monoallelic deletion of both the HER2 and TOP2A . The current study demonstrates the complex interrelationship between the HER2 and TOP2A genes in breast cancer. The clinical implications of TOP2A amplification and deletion in breast cancer need to be further defined. If TOP2A gene dosage can be confirmed to correlate with tumor responsiveness to anthracycline-based therapy in the clinical setting, FISH testing for TOP2A status may be warranted to aid in the selection of the most appropriate therapy.

Adenocarcinoma↗
PubMed2004

Nipple-sparing mastectomy: technique and results of 54 procedures.

HYPOTHESIS: The rationale for removal of the nipple-areolar complex (NAC) during total mastectomy centers on long-standing concerns about possible neoplastic involvement of the NAC and its postoperative viability. Nipple-sparing mastectomy (NSM) combines a skin-sparing mastectomy with preservation of the NAC, intraoperative pathological assessment of the nipple tissue core, and immediate reconstruction, thereby permitting better cosmesis for patients undergoing total mastectomy. Neoplastic involvement of the NAC can be predicted before surgery and assessed during the operation, and sustained postoperative viability of the NAC is likely with appropriate surgical technique. RESULTS: Fifty-four NSMs with immediate reconstruction were attempted among 44 patients. Six NAC core specimens revealed neoplastic involvement on frozen section analysis, resulting in conversion to total mastectomies. Forty-five of the 48 completed NSMs maintained postoperative viability of the NAC; 3 NACs had partial loss. CONCLUSION: Nipple-sparing mastectomy is a reasonable option for carefully screened patients.

Adult↗
PubMed2004

Prospective study of intraoperative mammary ductoscopy in patients undergoing partial mastectomy for breast cancer.

BACKGROUND: The purpose of this study was to critically evaluate the added benefit of intraoperative mammary ductoscopy on margin assessment and identification of occult intraductal pathology in patients undergoing therapeutic partial mastectomy for in-situ and invasive breast carcinoma. METHODS: Eligible patients underwent intraoperative mammary ductoscopy before partial mastectomy. In patients where an intraductal abnormality was identified and the mammary ductoscope was not within the partial mastectomy cavity, an additional ductoscopy-directed margin of tissue was analyzed. RESULTS: Nineteen of 30 (63%) patients yielded nipple aspirate fluid and were able to undergo mammary ductoscopy; an intraductal abnormality was identified in 15 of 19 (79%) patients. Only 1 patient had an occult infiltrating carcinoma, which was outside of the resection cavity and identified by ductoscopy. CONCLUSIONS: Although mammary ductoscopy can identify intraductal abnormalities during partial mastectomy in a significant number of patients, many of these findings may be either benign or within the standard field of resection, thus adding no benefit to the patient.

Breast Neoplasms↗
PubMed2003

Axillary lymph node metastases in patients with a final diagnosis of ductal carcinoma in situ.

BACKGROUND: Recent studies report the incidence of axillary metastases in patients with ductal carcinoma in-situ (DCIS) approaches 13%. The purpose of this study was to define the incidence of axillary micrometastases in patients with pure DCIS before and after the introduction of sentinel lymph node biopsy. METHODS: Patients with a final diagnosis of DCIS form the basis of this study. Data were entered prospectively into an Institutional Review Board approved Oracle database from January 1997 through July 2002. RESULTS: One hundred and thirty-four patients had lymph nodes evaluated. Ninety-eight percent of patients had no evidence of metastatic disease and 2% were found to have micrometastases. This was consistent in those who had level I or II lymph node sampling or both and those who had lymphatic mapping and a sentinel lymph node biopsy procedure. CONCLUSIONS: These data do not support axillary lymph node removal of any type in patients with pure DCIS.

Axilla↗
PubMed2003

Does ultrasound core breast biopsy predict histologic finding on excisional biopsy?

BACKGROUND: The purpose of this study was to determine whether ultrasound-guided core breast biopsy accurately predicts the histologic finding of a subsequent excisional procedure. METHODS: Data were collected prospectively from 1997 to 2001 for 832 ultrasound-guided core breast biopsies (USB) that were followed by excisional breast procedure (EP) within 1 year at our institution. The principal histologic finding obtained at USB and EP was identified for each procedure and the degree of agreement was assessed. RESULTS: The USB histology predicted EP histology in 90% (n = 746) of the procedures. The USB histology was more significant than EP histology in 3% (n = 22) of procedures; USB histology underdetermined EP histology in 7% (n = 64) of procedures. Overall, our results indicate moderate agreement between the principal histology identified at USB relative to that identified at EP. CONCLUSIONS: Ultrasound-guided core breast biopsy is an effective diagnostic method, but sampling limitations do exist.

Biopsy↗
PubMed2003

Does core needle breast biopsy accurately reflect breast pathology?

BACKGROUND: Core needle breast biopsy (CB) has replaced excisional biopsy as the initial diagnostic biopsy procedure for many suspicious breast lesions; however, CB remains a sampling procedure. The purpose of this study was to determine the degree of agreement between histology obtained at CB and that obtained at a subsequent excisional procedure (EP). We hypothesized a high degree of agreement. METHODS: Data were collected prospectively for 3035 CBs performed by breast radiologists using either ultrasound or stereotactic guidance between January 1995 and July 2002, 1410 (46%) of which had a subsequent EP within 1 year. Histologic categories were defined as invasive breast cancer, duct carcinoma in-situ, atypia/lobular carcinoma in-situ, and benign. The principal histology (PH) from CB and EP was identified and compared. RESULTS: Overall, there was moderate agreement (kappa=0.669) between CB and EP histology. Complete agreement occurred in 1168 (83%) procedures. For the remaining 242, the PH was identified only at CB for 78 (5%) procedures, and only after EP for 164 (12%) procedures. CONCLUSIONS: Although the majority (83%) of CB and EP demonstrated exact histologic agreement, CB was diagnostic for 1246 (88%) procedures.

Biopsy↗
PubMed2002

A prospective review of the decline of excisional breast biopsy.

BACKGROUND: Although excisional breast biopsy has long been considered the standard for breast cancer diagnosis, core biopsies are now used more frequently. Whether core biopsy can eventually replace excisional biopsy remains unknown. The purpose of this study was to evaluate the relationship between diagnostic excisional and core biopsies relative to surgical treatment procedures. METHODS: We analyzed our data collected prospectively from 1995 through 2000, which included inpatient and outpatient surgical data, office visits, and radiology biopsy data including stereotactic, mammotome, and ultrasound core biopsies. The Cochran-Armitage trend test was used to assess the shift in diagnostic technique. RESULTS: From 1995 through 2000 there were 2,631 core biopsies performed, 2,685 excisional biopsies, 2,881 surgical procedures for breast cancer, and 51,109 office visits. Although the percentage of core biopsies relative to excisional biopsies increased from 31% to 68% (P <0.001), the percentage of biopsies relative to the number of office visits remained stable at 10% to 11%. The percentage of breast cancer procedures relative to office visits also remained stable at 5% to 6%. CONCLUSIONS: Our data indicate that core biopsies are being performed more often than excisional biopsies. Nevertheless, one in three biopsies done at our institution is excisional.

Biopsy↗