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Stuart J Schnitt

Publications and source records attributed to Stuart J Schnitt.

At least 37 records · Page 2Linked to original sources
PubMed2005

Bimodal frequency distribution of estrogen receptor immunohistochemical staining results in breast cancer: an analysis of 825 cases.

Immunohistochemical analysis is used routinely to determine the estrogen receptor (ER) status of breast cancers in paraffin sections. However, lack of standardization has raised concerns that weakly ER+ tumors often are classified erroneously as ER-. To determine the frequency of weakly ER+ tumors, we reviewed ER immunostains of 825 breast cancers. For each case, we estimated the proportion of ER+ tumor cells and also determined an Allred score (which results in scores of 0 or 2 through 8, based on staining intensity and proportion of positive cells). In 817 cases (99.0%), tumor cells showed complete absence of staining or staining in 70% or more of the cells. Similarly, 818 cases (99.2%) exhibited Allred scores of 0 or of 7 or 8. Thus, with the immunohistochemical method used in our laboratory, ER staining is essentially bimodal. The overwhelming majority of breast cancers are either completely ER- or unambiguously ER+, and cases with weak ER immunostaining are rare.

Breast Neoplasms↗
PubMed2004

Magnetic resonance imaging of the breast prior to biopsy.

CONTEXT: Breast magnetic resonance imaging (MRI) has been shown to have high sensitivity for cancer detection and is increasingly used following mammography to evaluate suspicious breast lesions. OBJECTIVE: To determine the accuracy of breast MRI in conjunction with mammography for the detection of breast cancer in patients with suspicious mammographic or clinical findings. DESIGN, SETTING, AND PATIENTS: Prospective multicenter investigation of the International Breast MR Consortium conducted at 14 university hospitals in North America and Europe from June 2, 1998, through October 31, 2001, of 821 patients referred for breast biopsy for American College of Radiology category 4 or 5 mammographic assessment or suspicious clinical or ultrasound finding. INTERVENTIONS: MRI examinations performed prior to breast biopsy; MRI results were interpreted at each site, which were blinded to pathological results. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of breast MRI. RESULTS: Among the 821 patients, there were 404 malignant index lesions, of which 63 were ductal carcinoma in situ (DCIS) and 341 were invasive carcinoma. Of the 417 nonmalignant index lesions, 366 were benign, 47 showed atypical histology, and 4 were lobular carcinoma in situ. The AUC pooled over all institutions was 0.88 (95% confidence interval [CI], 0.86-0.91). MRI correctly detected cancer in 356 of 404 cancer cases (DCIS or invasive cancer), resulting in a sensitivity of 88.1% (95% CI, 84.6%-91.1%), and correctly identified as negative for cancer 281 of 417 cases without cancer, resulting in a specificity of 67.7% (95% CI, 62.7%-71.9%). MRI performance was not significantly affected by mammographic breast density, tumor histology, or menopausal status. The positive predictive values for 356 of 492 patients was 72.4% (95% CI, 68.2%-76.3%) and of mammography for 367 of 695 patients was 52.8% (95% CI, 49.0%-56.6%) (P<.005). Dynamic MRI did not improve the AUC compared with 3-dimensional MRI alone, but the specificity of a washout pattern for 123 of 136 patients without cancer was 90.4% (95% CI, 84%-95%). CONCLUSIONS: Breast MRI has high sensitivity but only moderate specificity independent of breast density, tumor type, and menopausal status. Although the positive predictive value of MRI is greater than mammography, MRI does not obviate the need for subsequent tissue sampling in this setting.

Adult↗
PubMed2004

Association of hormone replacement therapy to estrogen and progesterone receptor status in invasive breast carcinoma.

BACKGROUND: Observational studies and randomized trials have demonstrated that hormone replacement therapy (HRT) increases the recipient's risk of developing breast carcinoma. Because it is known that some breast malignancies are hormonally responsive and that others are not, it has been hypothesized that HRT may be associated with the development of estrogen receptor (ER)-positive/progesterone receptor (PR)-positive breast carcinoma more so than with the development of ER-negative/PR-negative breast carcinoma. METHODS: The Nurses' Health Study is a prospective cohort study that enrolled 121,700 female registered nurses ages 30-55 years in 1976. In the current study, the authors analyzed 2548 malignancies that developed among eligible postmenopausal women in that cohort between 1980 and 2000 and for which data on ER and PR status were available. RESULTS: Compared with women who had never used HRT, current long-term users of HRT were more likely to develop ER-positive/PR-positive breast carcinoma (multivariate risk ratio [RR], 1.80; 95% confidence interval [CI], 1.52-2.12) but were not any more likely to develop ER-negative/PR-negative disease (multivariate RR, 1.00; 95% CI, 0.72-1.39). This effect grew stronger with increasing duration of current HRT use and was also more pronounced among women with body mass index < 25 kg/m2. Furthermore, the association between HRT use and ER-positive/PR-positive disease was stronger among patients receiving combined HRT (CHRT) regimens, which included estrogen and progesterone, than among users of estrogen alone (ERT). In addition, tumors tended to develop more quickly in current users of CHRT than in ERT users. CONCLUSIONS: The finding that current users of HRT were more likely to develop ER-positive/PR-positive tumors than they were to develop ER-negative/PR-negative ones suggests that both endogenous and exogenous hormonal factors may influence breast tumor characteristics. In analyses of the effects of hormonal factors on breast tumor development, ER-positive/PR-positive tumors and ER-negative/PR-negative tumors should be considered separately from each other.

Adult↗
PubMed2004

Outcome after breast-conserving therapy for patients with stage I or II mucinous, medullary, or tubular breast carcinoma.

PURPOSE: To evaluate the site of first failure of patients with early-stage tubular, mucinous, and medullary breast carcinoma after breast-conserving therapy and compare their results with those of patients with infiltrating ductal carcinoma (IDC). METHODS AND MATERIALS: Twenty clinical Stage I and II patients with mucinous carcinoma, 27 with medullary carcinoma, 28 with tubular carcinoma, and 1055 with IDC were identified. The minimal potential follow-up was 10 years. RESULTS: No statistically significant difference (p = 0.15) was seen in the site of first failure between the four histologic types within the first 10 years after treatment. When the IDC tumors were omitted from the comparison, the failure patterns of the remaining three histologic types were not significantly different (p = 0.31). In a polychotomous logistic model, histologic type was not significantly associated with the site of first failure (all p >0.17). Local failure was significantly associated with age <50 years (p = 0.04), positive surgical margins (p = 0.007), lymphovascular invasion (p = 0.04), and tumors with an extensive intraductal component (p <0.001). Regional/distant/opposite breast failure was significantly associated with clinical Stage T2 tumors (p <0.001), four or more positive lymph nodes (p = 0.004), and lymphovascular invasion-positive tumors (p <0.001). Second malignancy or death was significantly associated with age at diagnosis >60 years (p <0.001) and lymphovascular invasion-positive tumors (p = 0.03). CONCLUSION: No statistically significant difference was noted in the site of first failure between patients with medullary, mucinous, or tubular carcinoma and patients with IDC. Although not statistically significant, we did note a trend toward a lower long-term rate of disease-free survival in patients with IDC.

Adenocarcinoma↗
PubMed2004

HER-2 testing and trastuzumab therapy for metastatic breast cancer: a cost-effectiveness analysis.

PURPOSE: Trastuzumab therapy has been shown to benefit metastatic breast cancer patients whose tumors exhibit HER-2 protein overexpression or gene amplification. Several tests of varying accuracy and cost are available to identify candidates for trastuzumab. We estimated the cost-effectiveness of alternative HER-2 testing and trastuzumab treatment strategies. PATIENTS AND METHODS: We performed a decision analysis using a state-transition model to simulate clinical practice in a hypothetical cohort of 65-year-old metastatic breast cancer patients. Outcomes were quality-adjusted life-years (QALYs), lifetime cost, and incremental cost-effectiveness ratio (ICER). Interventions included testing with the HercepTest (DAKO, Carpinteria, CA) immunohistochemical assay alone, fluorescence in situ hybridization (FISH) alone, and both tests, followed by trastuzumab and chemotherapy for patients with positive test results and chemotherapy alone for patients with negative test results. RESULTS: In the base case, initial HercepTest with FISH confirmation of all positive results had an ICER of $125,000 per QALY gained. The incremental cost-effectiveness of initial FISH was $145,000 per QALY gained. Other strategies yielded the same or poorer effectiveness at a higher cost, or lower effectiveness at a lower cost, but with a less favorable ICER. These findings persisted under a range of assumptions, and only changes in test characteristics substantially altered results. CONCLUSION: It is more cost-effective to use FISH alone or as confirmation of all positive HercepTest results, rather than using FISH to confirm only weakly positive results or using HercepTest alone. When multiple tests are available to identify treatment candidates, test characteristics may have a substantial impact on the aggregate costs and effectiveness of treatment.

Aged↗
PubMed2004

Diagnostic agreement in the evaluation of image-guided breast core needle biopsies: results from a randomized clinical trial.

BACKGROUND: Image-guided core needle biopsies (CNBs) are commonly used as the initial sampling method for nonpalpable, mammographically detected breast lesions. Although prior studies have shown that this procedure is a highly sensitive and accurate method for the detection of breast cancer, the level of diagnostic agreement between pathologists in the analysis of CNB has not been previously studied in detail. METHODS: To address this, we reviewed the pathologic findings in 2004 CNB from patients enrolled in the Radiologic Diagnostic Oncology Group 5 study, a randomized, multicenter trial designed to determine the role of CNB and fine needle aspiration biopsy in the evaluation of nonpalpable breast lesions. Slides of CNB specimens were initially diagnosed by pathologists at the 22 participating institutions (local diagnosis) and were then sent to the study pathologists for central review (central diagnosis). Local and central diagnoses were compared. RESULTS: Overall, the central diagnosis and local diagnosis were concordant in 1925 cases (96%), indicating an excellent level of agreement by kappa statistic analysis (kappa = 0.90; 95% confidence interval 0.88-0.92). The level of agreement between local and central pathologists did not vary with the image guidance system (stereotactic mammography vs. ultrasound) or with the mammographic findings (soft tissue density vs. microcalcifications). The level of diagnostic agreement observed for CNB was comparable to that observed among 596 open surgical biopsies obtained from patients in this study and subjected to central pathology review (93% agreement; kappa = 0.89, 95% confidence interval 0.86-0.92). CONCLUSIONS: The level of diagnostic agreement in interpretation of breast CNB is extremely high among pathologists and is comparable to that seen for open surgical biopsy.

Biopsy, Needle↗
PubMed2004

A prospective study of diet and benign breast disease.

Much attention has been paid to the relation between diet and breast cancer risk. Because benign breast disease (BBD), particularly atypical hyperplasia (AH), is a marker of increased breast cancer risk, studies of diet and BBD may provide evidence about the effect of diet at an early stage in the process of breast carcinogenesis. We evaluated the relationship between fat, fiber, antioxidant and caffeine intake and incidence of non-proliferative BBD, proliferative BBD without atypia and AH in the Nurses' Health Study II. We calculated rate ratios (RR) and 95% confidence intervals (95% CI) for each quartile of energy-adjusted intake using the lowest quartile as reference. There was no increase in risk of BBD with increasing fat intake, rather increasing vegetable fat was associated with a significant reduction in the rate of proliferative BBD without atypia. There was no significant association between any type of BBD and micronutrient intake. High caffeine consumption was positively associated (RR = 2.46, 95% CI 1.11-5.49 for the highest quartile), and use of multivitamin supplements inversely associated (RR = 0.57, 95% CI 0.33-0.98) with risk of AH although these analyses were based on small numbers. These data do not support the hypothesis that higher fat consumption increases risk of BBD, with or without atypia, and also provide little evidence for a major role of antioxidants in the development of breast disease. They do, however, raise the possibility that high caffeine intake may increase, and use of vitamin supplements may decrease risk of developing AH.

Adult↗
PubMed2003

The diagnosis and management of pre-invasive breast disease: flat epithelial atypia--classification, pathologic features and clinical significance.

Flat epithelial atypia is a descriptive term that encompasses lesions of the breast terminal duct lobular units in which variably dilated acini are lined by one to several layers of epithelial cells, which are usually columnar in shape and which display low-grade cytologic atypia. Observational studies have suggested that at least some of these lesions may represent either a precursor of ductal carcinoma in situ (DCIS) or the earliest morphological manifestation of DCIS. In contrast, the limited available clinical follow-up data suggest that the risk of both local recurrence and progression of these lesions to invasive cancer is extremely low, supporting the notion that categorizing such lesions as 'clinging carcinoma' and managing them as if they were fully developed DCIS will result in overtreatment of many patients. Additional studies are needed to better understand the biological nature and clinical significance of these lesions.

Breast↗
PubMed2003

Benign breast disease and breast cancer risk: morphology and beyond.

Evidence from clinical follow-up studies has indicated that there is a relationship between the presence of histologically proven benign breast disease and breast cancer risk and that the level of risk varies according to the histologic category of benign breast disease. In particular, proliferative lesions without atypia are associated with a 1.5- to 2-fold increase in risk, whereas atypical hyperplasias are associated with a fourfold to fivefold increase in breast cancer risk. A number of clinical factors appear to modify the risk associated with these lesions, including the time since biopsy, menopausal status, and family history of breast cancer. Recent studies have begun to evaluate the potential role of biologic, molecular, and genetic markers in assessing breast cancer risk in patients with benign breast disease. Additional information derived from clinicopathologic follow-up studies, epidemiologic studies, and molecular and genetic studies will provide new insights into benign breast disease and breast cancer risk.

Breast↗
PubMed2003

Columnar cell lesions of the breast.

Columnar cell lesions of the breast represent a spectrum of lesions which have in common the presence of columnar epithelial cells lining variably dilated terminal duct lobular units, ranging from those that show little or no cytologic or architectural atypia to those that show sufficient cytologic and architectural features to warrant a diagnosis of atypical ductal hyperplasia or ductal carcinoma in situ. Recent studies have begun to provide insights into the biological nature and clinical significance of these lesions. In this article, we review the current state of knowledge and propose a simplified scheme for their classification.

Biomarkers, Tumor↗
PubMed2003

Adolescent diet and incidence of proliferative benign breast disease.

Studies of adult diet and risk of breast cancer have yielded mainly null results, but this does not rule out a possible impact of adolescent diet. This study examined associations between components of adolescent diet and risk of proliferative benign breast disease (BBD), a marker for breast cancer. The study population consisted of 29494 women in the Nurses' Health Study II who completed a questionnaire on adolescent diet in 1998 and who were 33-53 years of age at that time. A total of 470 new cases of proliferative BBD were identified between 1991 and 1997. Incidence rate ratios (RRs) and 95% confidence intervals (CIs) were calculated for quartiles of energy-adjusted intakes, using the lowest quartile of each as the reference group. Total fat intake during adolescence was unrelated to risk of proliferative BBD, although there were positive associations for intakes of animal fat and monounsaturated fat and an inverse association for intake of vegetable fat. For vitamin E intake, the multivariate RRs were 1.13, 0.88, and 0.79 (95% CI, 0.61-1.04) for women in the second, third, and highest quartiles, respectively (P for trend = 0.05). The multivariate RRs were 0.94, 0.99, and 0.75 (95% CI, 0.57-0.98) for women in increasing quartiles of fiber intake (P for trend = 0.05). Vegetable fat, vitamin E, and fiber intakes during adolescence were inversely associated with risk of proliferative BBD in this population. Confirmation of these associations may suggest a means for prevention of breast cancer.

Adolescent↗
PubMed2002

Family history of breast cancer, age and benign breast disease.

A major risk factor for breast cancer is having a first-degree family history of the disease. Benign breast disease (BBD), particularly atypical hyperplasia, is also associated with an increased risk of breast cancer. However, the relationship between family history of breast cancer and BBD is unclear. From 1989 through 1997, 80,995 participants in the Nurses' Health Study II were followed; 16,849 reported a first diagnosis of BBD. Pathology slides were reviewed for 1,465 women who reported having a tissue biopsy, and these were classified as nonproliferative BBD, proliferative BBD without atypia or atypical hyperplasia. Women with a family history of breast cancer were more likely to report a physician diagnosis of BBD [rate ratio (RR) = 1.38, 95% confidence interval (CI) 1.29-1.46]. The magnitude of this association declined with age from RR = 1.96 (95% CI 1.55-2.47) at 25-29 years to RR = 1.20 (95% CI 0.95-1.52) at age 45-50 years. Among women with proliferative disease, those with a family history of breast cancer were almost 3 times as likely to have atypia (prevalence odds ratio = 2.72, 95% CI 1.23-5.89) than those with no family history. In conclusion, women with a family history of breast cancer appear to be at increased risk of being diagnosed with BBD, in particular the high-risk types of BBD associated with a greatly increased risk of breast cancer. This link adds weight to the belief that BBD with atypia is a precursor or marker lesion for breast cancer.

Adult↗
PubMed2002

Radial scars of the breast and breast carcinomas have similar alterations in expression of factors involved in vascular stroma formation.

We recently reported that radial scars are an independent histologic risk factor for breast cancer. The reason for this association is not known. Given the importance of stromal-epithelial interactions in the pathogenesis of breast cancer, we studied radial scars for the expression of a number of factors known to be involved in the formation of vascular stroma in breast cancer. In situ hybridization was performed on formalin-fixed paraffin sections using (35)S-labeled riboprobes for collagen type 1, total fibronectin, extra domain A (ED-A)+ fibronectin, thrombospondin 1, vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF), and one of its endothelial receptors, kinase insert domain-containing receptor (KDR) (vascular endothelial growth factor receptor [VEGFR-2]). Expression levels in radial scars (9 cases) were compared with those in normal breast tissue (15 cases) and infiltrating ductal breast carcinoma (4 cases). Factor VIII-related antigen immunostaining was used to define the distribution of microvessels in radial scars, carcinoma, and normal breast tissue. Compared with normal breast tissue, the radial scars showed focally increased numbers of blood vessels and focally increased expression of messenger RNA (mRNA) for collagen type 1, total fibronectin, ED-A+ fibronectin, thrombospondin 1, VPF/VEGF, and KDR. This pattern of mRNA overexpression was similar to that seen in the 4 invasive cancers. We conclude that there are similarities between radial scars and invasive breast cancers with regard to the level of mRNA expression for several factors involved in the formation of vascular stroma. These results suggest that a similar disturbance in stromal-epithelial interactions is present in both lesions.

Adult↗
PubMed2002

Nonmalignant lesions in breast core needle biopsies: to excise or not to excise?

Large core needle biopsies using stereotactic mammography or ultrasound guidance are now commonly performed as the initial diagnostic approach to nonpalpable breast lesions. Although the subsequent management of patients with invasive cancer, ductal carcinoma in situ, and most benign lesions diagnosed on core needle biopsy specimens is straightforward, certain nonmalignant lesions pose dilemmas with regard to the most appropriate clinical management following core needle biopsy. The purpose of this article is to review the available data regarding several nonmalignant breast lesions, which when encountered in core needle biopsy specimens raise repeated management questions. These include atypical ductal hyperplasia, lobular neoplasia (atypical lobular hyperplasia and lobular carcinoma in situ), papillary lesions, radial scars, fibroepithelial lesions, mucocele-like lesions, and columnar cell lesions.

Biopsy, Needle↗
PubMed2002

(99m)Tc sestamibi breast imaging for the examination of patients with dense and fatty breasts: multicenter study.

PURPOSE: To evaluate the accuracy of scintimammography as an adjunct to physical examination and mammography in the detection of breast cancer in women with dense and fatty breasts. MATERIALS AND METHODS: A total of 558 women were prospectively enrolled from 42 centers in North America. Images were interpreted by readers blinded to the subjects' clinical history, mammographic findings, and other test results. The Breast Imaging Reporting and Data System classification was used to describe breast density. Parenchymal patterns of "heterogeneously dense" and "extremely dense" were used to classify breasts as dense, whereas "almost entirely fat" and "numerous vague densities" defined fatty breasts. Between-group differences were evaluated with the 2 test for categorical variables and Student t test for continuous variables. Accuracy of scintimammography was assessed against the core laboratory histopathologic evaluation, the standard. The 95% CIs around point estimates of sensitivity, specificity, and positive and negative predictive values were calculated with the normal approximation to the binomial distribution. RESULTS: The analyses were based on 580 breasts with an abnormality; 276 (48%) breasts were dense and 228 had a malignant lesion. Diagnostic properties for scintimammography of fatty versus dense breasts were, respectively, sensitivity, 72% versus 70%; specificity, 80% versus 78%; positive predictive value, 72% versus 67%; negative predictive value, 81% versus 81%; and accuracy, 77% versus 75% (all not significant). Scintimammography led to similar and significant changes in the posttest likelihood of cancer for both dense and fatty breasts. CONCLUSION: The diagnostic accuracy of scintimammography is not affected by breast density.

Adipose Tissue↗