PubMed Health⌕ Search

Biomedical subjects

James L Connolly

Publications and source records attributed to James L Connolly.

At least 19 recordsLinked to original sources
PubMed2007

Magnitude and laterality of breast cancer risk according to histologic type of atypical hyperplasia: results from the Nurses' Health Study.

BACKGROUND: Atypical hyperplasia (AH) in a benign breast biopsy is associated with an increased breast cancer risk. However, the influence of the histologic type of AH on the magnitude and laterality of breast cancer risk is poorly defined. METHODS: The authors conducted a case-control study of benign breast disease and breast cancer risk nested within the Nurses' Health Study (395 cases, 1610 controls). Benign breast biopsy slides were reviewed and categorized as showing nonproliferative lesions, proliferative lesions without atypia, or AH. Slides that showed AH were categorized further as atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH). RESULTS: The odds ratio (OR) for breast cancer among all women with AH was 4.1 (95% confidence interval [95% CI], 2.9-5.8). However, among premenopausal women, breast cancer risk was higher for women with ALH (OR, 7.3; 95% CI, 3.8-14.2) than for women with ADH (OR, 3.1; 95% CI, 2.0-4.8). Overall, 58.9% of invasive breast cancers that developed in women with AH were in the ipsilateral breast, and the frequency of ipsilateral breast cancer was similar for women with ALH (61.3%) and women with ADH (55.9%; P = .66). CONCLUSIONS: Women with AH in a benign breast biopsy were at a substantially increased risk for the development of breast cancer. Among premenopausal women, the risk appeared to be greater for those with ALH than those with ADH. Because only approximately 60% of cancers that develop in women with AH occur in the ipsilateral breast, for the purposes of clinical management, these lesions are viewed best as markers of a generalized (bilateral) increase in breast cancer risk.

Adolescent↗
PubMed2006

The influence of family history on breast cancer risk in women with biopsy-confirmed benign breast disease: results from the Nurses' Health Study.

BACKGROUND: An association between histologic category of benign breast disease (BBD) and breast cancer risk has been well documented. However, the influence of a positive family history (FH) on breast cancer risk among women with biopsy-confirmed BBD is less certain. METHODS: The authors conducted a nested case-control study of BBD and breast cancer risk among 2005 women who were enrolled in the Nurses' Health Study. Cases were women with breast cancer who had a previous benign breast biopsy (n = 395 women). Controls were women who also had previous biopsy-confirmed BBD but were free from breast cancer at the time the corresponding case was diagnosed (n = 1610 women). BBD slides were reviewed and categorized as either nonproliferative lesions, proliferative lesions without atypia, or atypical hyperplasia (AH). RESULTS: Compared with women who had nonproliferative lesions and no FH, women who had proliferative lesions without atypia and a positive FH had a higher breast cancer risk (odds ratio [OR], 2.45; 95% confidence interval [95% CI], 1.61-3.70) than women with no FH (OR, 1.51; 95% CI, 1.12-2.06; P = .07). Among women who had AH, the OR for the development of breast cancer was 4.38 (95% CI, 2.93-6.55) for those with no FH and 5.37 (95% CI, 3.01-9.58) for those with a positive FH (P = .57). There was no significant interaction between the type of BBD and FH (P = .74). CONCLUSIONS: A positive FH of breast cancer slightly increased the breast cancer risk among women who had proliferative lesions without atypia. The increase in risk of breast cancer associated with FH was not significant among women who had AH.

Adult↗
PubMed2006

Changes and problematic areas in interpretation of the AJCC Cancer Staging Manual, 6th Edition, for breast cancer.

CONTEXT: Tumor stage is an important prognostic factor and guides therapy for patients with breast cancer. The American Joint Committee on Cancer (AJCC) periodically updates the staging standards. This article describes changes and problematic areas in interpretation of the AJCC Cancer Staging Manual, 6th edition, for breast cancer and provides practical advice. OBJECTIVES: This article reviews the variety of practical problems that can arise during assessment of the pathologic stage and other prognostic/predictive factors included in the College of American Pathologists Checklist for Evaluation of Resected Breast Cancers. Potential practical difficulties that can arise include the classification of lymph nodes, for example, isolated tumor cells, micrometastases, metastases, and the combination of locations. Another difficult area is assignment of a correct size. The use of clinical and imaging studies for optimal pathologic staging is discussed. Finally, the proper use of the TNM descriptors is described. CONCLUSIONS: The various practical problems that can arise during the assessment of important prognostic and predictive features included in the College of American Pathologists Checklist for Evaluation of Resected Breast Cancers are discussed, and specific recommendations are given.

Breast Neoplasms↗
PubMed2005

Benign breast disease, recent alcohol consumption, and risk of breast cancer: a nested case-control study.

INTRODUCTION: Alcohol consumption is a well-established risk factor for breast cancer. Some studies have suggested that the risk of breast cancer associated with alcohol consumption is greater for women with a history of benign breast disease (BBD). We hypothesized that among women with biopsy-confirmed BBD, recent alcohol consumption would increase the risk of breast cancer in women with proliferative breast disease to a greater extent than in women with nonproliferative breast disease. METHODS: We conducted a nested case-control study in the Nurses' Health Study I and II. The cases (n = 282) were women diagnosed with incident breast cancer, with a prior biopsy-confirmed breast disease. The controls (n = 1,223) were participants with a previous BBD biopsy, but without a diagnosis of breast cancer. Pathologists reviewed benign breast biopsy slides in a blinded fashion and classified the BBD as nonproliferative, proliferative without atypia, or atypical hyperplasia, according to standard criteria. RESULTS: Women with nonproliferative breast disease consuming > or = 15 g of alcohol per day had a nonsignificant 67% increased risk of breast cancer (odds ratio = 1.67; 95% confidence interval 0.65 to 4.34) compared with nondrinkers. There was no evidence that recent alcohol consumption increased the risk of breast cancer to a greater extent in women with proliferative BBD than among women with nonproliferative BBD (P for interactio n = 0.20). CONCLUSION: Contrary to our a priori hypothesis, there was no evidence that recent alcohol consumption increased the risk of breast cancer to a greater extent among women with proliferative BBD than among women with nonproliferative BBD.

Adult↗
PubMed2005

Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy: results from the Nurses' Health Study.

BACKGROUND: Studies of patients with ductal carcinoma in situ (DCIS) "treated" by diagnostic biopsy alone have been rare, but provide important opportunities to gain insights into the natural history of these lesions. METHODS: During a review of 1877 breast biopsy specimens in a nested case-control study of benign breast disease and breast carcinoma risk, the authors identified 13 biopsy specimens with DCIS that were originally diagnosed as benign. Because each of these women was initially given a benign diagnosis, they received no treatment beyond the diagnostic biopsy. RESULTS: When compared with women with nonproliferative lesions, the odds ratio (OR) for the development of invasive breast carcinoma among those with retrospectively identified DCIS (n = 6) was 13.5 (95% confidence interval [CI], 3.7-49.7). The OR for the development of any subsequent invasive or in situ breast carcinoma event (n = 10) was 20.1 (95% CI, 6.1-66. 5). A retrospective review of these DCIS biopsy specimens revealed that the nuclear grade was low in four lesions, intermediate in six, and high in three. None showed comedo-type necrosis. Invasive carcinomas developed among women with DCIS of all nuclear grades. All 10 breast carcinoma events (100%) were in the ipsilateral breast. CONCLUSIONS: These results provided further evidence that patients with DCIS who received no treatment beyond a diagnostic biopsy were at substantially increased risk for developing ipsilateral invasive breast carcinoma, and that the increased risk in this setting was seen in DCIS of low, intermediate, and high nuclear grades.

Adult↗
PubMed2005

Ultrahigh-resolution and 3-dimensional optical coherence tomography ex vivo imaging of the large and small intestines.

BACKGROUND: Ultrahigh-resolution optical coherence tomography (OCT) has an axial resolution of <5 microm, 2 to 3 times finer than standard OCT. This study investigates ultrahigh-resolution and three-dimensional OCT for ex vivo imaging of the large and small intestines and correlates images with histology. METHODS: Ultrahigh-resolution OCT imaging was performed on fresh surgical specimens from the large and small intestines in the pathology laboratory, and images were correlated with histology. OCT was performed at 1.3-microm wavelength with 4.5-microm axial x 11-microm transverse resolution and at 1.1-microm wavelength with 3.5-microm axial x 6-microm transverse resolution. Three-dimensional OCT also was investigated. RESULTS: Normal and pathologic areas from 23 surgical specimens of the large and small intestines were imaged. Ultrahigh-resolution OCT distinguished the epithelial layer of the mucosa and visualized individual villi, glands, and crypts. Finer transverse resolutions improved visualization of features, e.g., the epithelium, but reduced the depth of field. Architectural distortion of glands from inflammatory and neoplastic processes was observed. Three-dimensional rendering enabled visualization of surface pit pattern and mucosal folds as well as subsurface crypt microstructure. CONCLUSIONS: This study evaluates new OCT technology and can provide a baseline for interpreting future ultrahigh-resolution endoscopic OCT studies.

Adult↗
PubMed2005

Universal newborn hearing screening: are we achieving the Joint Committee on Infant Hearing (JCIH) objectives?

OBJECTIVE: To determine whether a two-stage auditory brainstem response (ABR) Universal Newborn Hearing Screening (UNHS) protocol at an academic medical center has been achieving the Joint Committee on Infant Hearing (JCIH) recommendations for screening all infants, diagnosing hearing loss (HL) within 3 months, and instituting intervention within 6 months. STUDY DESIGN: Retrospective database and chart review in an academic tertiary care hospital. METHODS: A 5-year retrospective review of all newborns screened at our medical center between 1997 to 2001 was performed. Screening was performed by multiple in-hospital postnatal sequential ABR with follow-up outpatient ABR for failures. The protocol called for each newborn to receive at least two separate ABR in-hospital screenings before discharge if the newborn failed the initial screening. For those newborns with extended hospital courses, additional ABR screening were performed randomly in attempt to decrease referral rates at time of discharge. Overall screening population capture rate, referral rate, and false-positive rate were calculated. In addition, HL risk factors, age at diagnosis of HL, and age of onset of intervention were obtained. Cost per diagnosis of HL was calculated as well. RESULTS: The total number screened was 17,602. Seventy-eight (0.44%) were diagnosed with HL, with 62 (79%) in the high-risk population. The frequency of HL was 1 per 811 low-risk neonates versus 1 in 75 meeting high-risk criteria. Overall population capture rate was greater than 99%, referral rate 4.1%, and false-positive rate 3.6%. Mean age at diagnosis was 3.9 months, with mean age at intervention 6.1 months. Cost per diagnosis was estimated at US 5,074 dollars. CONCLUSIONS: Our current UNHS protocol using sequential ABR has been successful in screening virtually all neonates and providing timely intervention. This retrospective review has shown one HL diagnosis for every 811 babies screened without high-risk factors.

Academic Medical Centers↗
PubMed2005

Early life factors and incidence of proliferative benign breast disease.

Proliferative benign breast disease is a marker of increased breast cancer risk, yet little is known about its etiology. Most studies of benign breast disease have focused only on risk factors in adulthood, despite growing evidence that factors in early life influence breast cancer risk. We explored the relations of several early life factors with incidence of proliferative benign breast disease among 71,896 premenopausal women in the Nurses' Health Study II who recalled their body fatness at young ages, physical activity in adolescence, birthweight, and history of being breastfed. Between 1991 and 1997, 901 of these women were identified as having proliferative benign breast disease from a centralized pathology review. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazards models. Greater childhood body fatness (ages 5-10) was associated with decreased risk of proliferative benign breast disease; the multivariate RR (95% CI) for the most overweight compared with the most lean was 0.61 (0.44-0.86; P(trend) < 0.0001) and remained significant after adjustment for current body mass index. Body mass index at age 18 was also inversely associated with incidence of proliferative benign breast disease, with a multivariate RR (95% CI) of 0.67 (0.52-0.88) for those who were > or =25 kg/m(2) compared with those who were <19 kg/m(2) (P(trend) = 0.001). There were no clear associations for physical activity in adolescence, birthweight, or being breastfed. These results indicate that premenopausal women who were heavier at young ages have lower incidence of proliferative benign breast disease, consistent with previous findings for breast cancer.

Adiposity↗
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

High-resolution imaging of the thyroid gland using optical coherence tomography.

BACKGROUND: Current diagnostic imaging modalities of the thyroid gland cannot reliably distinguish benign from malignant lesions, primarily because of their inability to visualize microscopic structure. A high-resolution imaging technique capable of examining thyroid tissue architectural morphology in real time is needed. Optical coherence tomography (OCT) has been shown to achieve high resolutions approaching the cellular range (1-15 microm). The feasibility of optical coherence tomography for imaging thyroid tissue was explored ex vivo on the human thyroid gland. METHODS: High-resolution OCT was performed in real time at 2 to 4 frames per second on three postmortem and 15 surgically excised thyroid glands containing normal, hyperplastic, and neoplastic tissue. OCT images acquired were compared with those obtained using standard histopathologic methods. RESULTS: The microstructure of the normal thyroid gland, including colloid-filled follicles as small as 15 microm and their supporting stroma, was clearly identified. OCT images of degenerative, hyperplastic, adenomatous, and malignant change within the thyroid gland were shown to correlate well with corresponding histopathologic findings. CONCLUSIONS: The ability of OCT to image thyroid tissue microarchitecture makes it a potentially powerful technology that can be used to assess the thyroid gland at a resolution greater than currently available clinical imaging modalities.

Adult↗
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

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

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↗