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Teresa Wagner

Publications and source records attributed to Teresa Wagner.

At least 19 recordsLinked to original sources

Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation.

CONTEXT: Women with BRCA1 or BRCA2 mutation are often advised to undergo preventive oophorectomy. The effectiveness of this intervention has not been prospectively evaluated in a large cohort. OBJECTIVES: To estimate the incidence of ovarian, fallopian tube, and primary peritoneal cancer in women who carry a deleterious mutation in BRCA1 or BRCA2. To estimate the reduction in risk of these cancers associated with a bilateral prophylactic salpingo-oophorectomy. DESIGN, SETTING, AND PARTICIPANTS: Women known to carry a BRCA1 or BRCA2 mutation were identified from an international registry between 1992 and 2003. A total of 1828 carriers at 1 of 32 centers in Canada, the United States, Europe, and Israel completed questionnaires at baseline and follow-up. Participants were observed from the date of study entry until: diagnosis of ovarian, fallopian tube, or peritoneal cancer; death; or the date of the most recent follow-up. INTERVENTION: Participants were divided into women who had undergone bilateral prophylactic oophorectomy and those who had not. MAIN OUTCOME MEASURE: The incidence of ovarian, peritoneal, and fallopian tube cancer was determined by survival analysis. The risk reduction associated with prophylactic salpingo-oophorectomy was evaluated by a time-dependent survival analysis, adjusting for covariates. RESULTS: After a mean follow-up of 3.5 years, 50 incident ovarian, fallopian tube, and peritoneal cancer cases were reported in the cohort. Of the 1828 women, 555 (30%) underwent a bilateral prophylactic salpingo-oophorectomy prior to study entry, 490 (27%) underwent the procedure after entering the study, and 783 (43%) did not undergo the procedure. There were 32 incident cancers diagnosed in women with intact ovaries (1015/100,000 per year). Eleven cancer cases were identified at the time of prophylactic oophorectomy and 7 were diagnosed following prophylactic oophorectomy (217/100,000 per year). The estimated cumulative incidence of peritoneal cancer is 4.3% at 20 years after oophorectomy. The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80% (multivariate hazard ratio = 0.20; 95% confidence interval, 0.07-0.58; P = .003). CONCLUSION: Oophorectomy is associated with reduced risk of ovarian and fallopian tube cancer in high-risk women, although there is a substantial residual risk for peritoneal cancer in BRCA1 and BRCA2 mutation carriers following prophylactic salpingo-oophorectomy.

Adult↗

Effect of chest X-rays on the risk of breast cancer among BRCA1/2 mutation carriers in the international BRCA1/2 carrier cohort study: a report from the EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators' Group.

PURPOSE: Women who carry germline mutations in the BRCA1 and BRCA2 genes are at greatly increased risk of breast cancer (BC). Numerous studies have shown that moderate to high doses of ionizing radiation are a risk factor for BC. Because of the role of the BRCA proteins in DNA repair, we hypothesized that BRCA carriers might be more sensitive to ionizing radiation than women in the general population. PATIENTS AND METHODS: A retrospective cohort study of 1,601 female BRCA1/2 carriers was performed. Risk of breast cancer from exposure to chest x-rays, as assessed by questionnaire data, was analyzed using a weighted Cox proportional hazards model. RESULTS: In this cohort, any reported exposure to chest x-rays was associated with an increased risk of BC (hazard ratio [HR] = 1.54; P = .007). This risk was increased in carrier women aged 40 years and younger (HR = 1.97; P < .001) and in women born after 1949 (HR = 2.56; P < .001), particularly those exposed only before the age of 20 years (HR = 4.64; P < .001). CONCLUSION: In our series of BRCA carriers, we detected a relatively large effect on BC risk with a level of radiation exposure that is at least an order of magnitude lower than in previously studied medical radiation-exposed cohorts. Although part of this increase may be attributable to recall bias, the observed patterns of risk in terms of age at exposure and attained age are consistent with those found in previous studies. If confirmed, the results have important implications for the use of x-ray imaging in young BRCA1/2 carriers.

Adult↗

The relationship of myocardial bridges to coronary artery dominance in the adult human heart.

Myocardial bridging is recognized as an anatomical variation of the human coronary circulation in which an epicardial artery lies in the myocardium for part of its course. Thus, the vessel is 'bridged' by myocardium. The anterior interventricular branch of the left coronary artery has been reported as the most common site of myocardial bridges but other locations have been reported. The purpose of this study was to provide more definitive information on the vessels with myocardial bridges, the length and depth of the bridged segment, and the relationship between the presence of bridges and coronary dominance. Two hundred formalin-fixed human hearts were examined. Myocardial bridges were found in 69 (34.5%) of the hearts with a total of 81 bridges. One bridge was found in 59 of these hearts and multiple bridges were observed in ten (eight with double bridges and two with triple bridges). Bridges were most often found over the anterior interventricular artery (35 hearts). Bridges were also found over the diagonal branch of the left coronary artery (14), over the left marginal branch (five) and over the inferior interventricular branch of the left coronary artery (six). Bridges were also found over the right coronary artery (15 hearts), over the right marginal branch (four) and over the inferior interventricular branch of the right coronary artery (two). The presence of bridges appeared to be related to coronary dominance, especially in the left coronary circulation. Forty-six (66.6%) of the hearts with bridges were left dominant. Forty-two of these had bridges over the left coronary circulation and four over the right coronary circulation. Seventeen hearts (24.6%) were right dominant. Eleven of these had bridges over the right coronary circulation and six over the left coronary circulation. The remaining six hearts were co-dominant with four having bridges over the left coronary circulation and two over the right coronary circulation. The mean length of the bridges was 31 mm and the mean depth was 12 mm. The possible clinical implications of myocardial bridging may vary from protection against atherosclerosis to systolic vessel compression and resultant myocardial ischaemia.

Adult↗

[Primary tracheobronchial amyloidosis].

The primary tracheo-bronchial amyloidosis is a rare entity with long lasting and progressive course. Precise diagnosis can be established on the basis of pathological features seen in samples derived from the airways, obtained during fibreoptic bronchoscopy or during lung biopsy sometimes. Describing the case of an insidious course of primary tracheobronchial AL type amyloidoisis, that was initially recognised and treated as a chronic obstructive pulmonary disease. The authors represent its clinical course and the diagnostic difficulties. The changes in the respiratory tract, both radiological and endoscopic suggested a tuberculous or proliferative process. They were responsible for a severe increasing dyspnoea, due to bronchial obstruction, with muco-haemoptic expectoration. A forceps resection of the endobronchial lesions enabled to established the right diagnosis and further treatment limited to local procedures.

Amyloidosis↗

Assessment of the inflammatory process by endomyocardial biopsy in patients with dilated cardiomyopathy based on pathological and immunohistochemical methods.

INTRODUCTION: Myocarditis may lead to dilated cardiomyopathy (DCM) in immunogenetically predisposed individuals. The diagnosis of myocardial inflammation is currently based on histopathological and immunohistochemical methods. Previous studies indicate that inflammatory cardiomyopathy occurs in approximately 50% of patients with DCM. AIM: The goal of the study was to assess the inflammatory process in patients with DCM by endomyocardial biopsy using histopathological and immunohistochemical methods. METHODS: Endomyocardial biopsy specimens was examined using routine histopathological methods and immunochemical staining for T lymphocytes (CD3(+), n=84), major histocompatibility complex I (HLA ABC, n=48) and II (HLA DPQR, n=84) antigens and the adhesion molecules ICAM-1 (n=51) and VCAM-1 (n=48) in 84 patients (69 male, 15 female; mean age 35.0+/-10.5 years) with angiographically-confirmed DCM. Familial disease occurrence was noted in 14 (16.7%) patients. Cardiac samples obtained from 18 patients who died of non-cardiovascular causes were used as a control group. RESULTS: Myocarditis was diagnosed, according to the Dallas criteria, in 8 (9.5%) patients. The frequency of inflammatory cardiomyopathy, defined as the presence of >2 CD3(+) T lymphocytes per high-power field (hpf) in myocardial biopsy, was 14.3%. When broader criteria were applied (presence of >2.0 CD3(+) lymphocytes/hpf and/or 1.5 CD3(+) lymphocytes/hpf in multiple foci and increased expression of class I/II HLA), inflammatory cardiomyopathy was diagnosed in 32.1% of patients. Inflammatory activation of the endothelium, indicated by increased expression of at least three adhesion molecules (class I and II HLA, ICAM-1, VCAM-1), was present in 22 (45.8%) patients. The expression of HLA DPQR, HLA ABC and ICAM-1 was observed on the endothelium of capillaries and larger vessels, interstitial cells, and the surface of activated lymphocytes; immunohistochemical reactions were diffuse. In patients with markedly elevated expression of the aforementioned adhesion molecules, the expression was also present on cardiomyocyte cell membranes. VCAM-1 was restricted to the endothelium of individual small veins. The control group did not demonstrate any signs of myocarditis, inflammatory cardiomyopathy or inflammatory endothelial activation. CONCLUSIONS: The application of immunohistochemical methods to myocardial biopsy in order to identify the inflammatory cell phenotype and the presence of adhesion molecules permits the diagnosis of inflammatory cardiomyopathy in 14% or 32% of patients, depending on the criteria used, while conventional pathology allows for this diagnosis in 9% of patients. The observed frequency of inflammatory cardiomyopathy, defined as the presence of >2 CD3(+) T lymphocytes/hpf in the myocardium, was lower (14%) than in previous studies, while the frequency of inflammatory endothelial activation was similar (45%).

Adult↗

[Myocardial microabscesses detected by endomyocardial biopsy in a patient with dilated cardiomyopathy and celiac disease: a case report].

A case of an 18-year-old male with a one-month history of progressive heart failure and suspected viral myocarditis is presented. Myocardial biopsy revealed mononuclear infiltration and the presence of granulocytes with micro-abscesses. Small bowel biopsy and autoimmunological examinations documented the presence of celiac disease. The patient's condition gradually improved following antibiotics, standard heart failure treatment, dental caries therapy and introduction of gluten-free diet.

Abscess↗

Dilated cardiomyopathy caused by LMNA mutations. Clinical and morphological studies.

BACKGROUND: Dilated cardiomyopathy (DCM) is familial in about 20-35% of patients. The most frequently encountered mutations associated with DCM are found in LMNA. AIM: To define the frequency of LMNA mutations in a series of consecutive DCM patients and to evaluate the phenotype of mutation carriers. METHODS: We screened the 12 exons of LMNA in a series of 61 Polish patients with DCM diagnosed angiographically, as well as in two DCM families. RESULTS: Two mutations were detected in 5 mutation carriers (D192G in one proband and Y481Stop in one proband and 3 of his offspring), which represents 3.3% (2/61) of the DCM patients. These mutations were absent from 100 controls. The D192G mutation was found in a 26-year-old patient with mild DCM and heart failure leading to death within two years after onset of symptoms. Mild conduction disease was also present. Ultrastructural analysis of the endomyocardial biopsy showed a striking alteration of nuclear morphology. This finding can explain nuclear fragility and is in agreement with the pathophysiological mechanical hypothesis of LMNA mutations. All four Y481Stop mutation-carriers were affected. Three phenotypes were found: in the proband, cardiac dysrhythmia and pacemaker requirement preceded DCM leading to heart transplantation; the proband's 13-year old daughter had conduction disease (2nd degree A-V block) with subtle skeletal muscle involvement documented by immunofluorescence study; ventricular arrhythmia was detected in the proband's son at the age of 11 and in the proband's daughter at the age of 18. Serum creatine kinase was normal in all mutation carriers.

Adolescent↗

[Clinico-pathological collations in borreliosis].

Borreliosis is an infectious disease caused by spirochetal microorganisms Borrelia burgdorferi transmitted by ticks. Due to versatile clinical symptomatology and many pathogenetic aspects not explained yet, diagnosis of this disease is often very difficult. Borreliosis may affect various human organs and systems such as movement system, nervous system (central and peripheral), skin, heart and vessels. One of the diagnostic methods for detection of microbial organisms in tissues is the histochemical staining by Warthin-Starry. Very important problem connected with this illness is the relationship between borrelial antigens and autoimmunity.

Humans↗

[Reversible dilated cardiomyopathy in a patient with acute, advanced heart failure and intense endothelial inflammatory reaction in endomyocardial biopsy--a case report].

Inflammatory response of the endothelium has been increasingly recognized in the aetiopathogenesis of sporadic dilated cardiomyopathy (DCM). It has been shown that up to 2/3 of patients with DCM have immunohistological evidence of enhanced activation of the endothelium. We present a case of a middle-aged patient with a history of hypertension and hyperlipidaemia who developed sudden significant left ventricular dysfunction following flu-like syndrome. Endomyocardial biopsy revealed no myocarditis, but immunohistological features of endothelial activation were present. Additionally, increasing titers of IgG antibodies against PvB19 were observed. During 18 months of standard heart failure treatment along with statin therapy, we observed a significant recovery of left ventricular systolic function, and in this way, reversible dilated cardiomyopathy.

Biopsy↗

Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers.

Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth = 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.

Adolescent↗

Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study.

PURPOSE: The purpose of this study was to estimate the extent of protection offered against breast cancer by prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations and to determine to what extent risk reduction varies with age at oophorectomy, age at diagnosis, and time elapsed since surgery. PATIENTS AND METHODS: We analyzed 1,439 patients with breast cancer and 1,866 matched controls derived from a registry of BRCA1 and BRCA2 carriers. We estimated odds ratios (ORs) of breast cancer for having had a bilateral oophorectomy, using conditional logistic regression, matched for parity and for oral contraceptive use. RESULTS: A previous history of oophorectomy was associated with a significant reduction in breast cancer risk of 56% for BRCA1 carriers (OR = 0.44; 95% CI, 0.29 to 0.66) and of 46% for BRCA2 carriers (OR = 0.57; 95% CI, 0.28 to 1.15). The risk reduction was greater if the oophorectomy was performed before age 40 (OR = 0.36; 95% CI, 0.20 to 0.64 for BRCA1 carriers) than after age 40 (OR = 0.53; 95% CI, 0.30 to 0.91). The protective effect was evident for 15 years post-oophorectomy (OR = 0.39; 95% CI, 0.26 to 0.57). CONCLUSION: Oophorectomy is an effective means of reducing the risk of breast cancer in carriers of BRCA1 mutations. The data suggest oophorectomy is protective in BRCA2 carriers as well, but needs to be confirmed in other studies.

Adult↗

Lesion miss rates and false-negative rates for 1115 consecutive cases of stereotactically guided needle-localized open breast biopsy with long-term follow-up.

PURPOSE: To retrospectively determine the lesion miss rate and false-negative rate of needle-localized open breast biopsy (NLOBB) with stereotactic guidance in a large study population. MATERIALS AND METHODS: The ethical review board approved the study; the need for informed consent was waived. A total of 1115 stereotactic NLOBBs performed in 1068 women aged 22-90 years (mean age, 54 years) were tracked to determine outcomes. In cases of malignancy, NLOBB was considered to be diagnostically successful. The mammographic outcomes in all patients with benign results at NLOBB were tracked for at least 2 years. Cases without such mammographic follow-up were cross-referenced with a tumor registry after at least 54 months. The lesion miss rate was based on all malignant lesions and all lesions with long-term mammographic follow-up. Results from all 1115 NLOBBs were used to report the false-negative rate. RESULTS: Of 1115 NLOBBs, 472 (42%) had malignant results. Mammographic follow-up data were available for 535 (83%) of 643 NLOBBs with benign results. Mammographic follow-up revealed 11 lesions that were missed with NLOBB, of which five were malignant and six benign. Thus, the lesion miss rate with NLOBB was 1.1% (11/[472 + 535]). Among the 643 cases, in 108 of them without mammographic follow-up (17%), cross-referencing with a tumor registry did not reveal missed cases of breast carcinoma. The false-negative rate was therefore 1.0% (5/[472 + 5]). CONCLUSION: On the basis of the results of long-term follow-up, the authors noted a lesion miss rate of 1.1% and a false-negative rate of 1.0%, which indicate that NLOBB with stereotactic guidance is an accurate method for diagnosing breast lesions.

Adult↗

An anatomical classification of the variations of the inferior phrenic vein.

The majority of anatomical textbooks of gross anatomy offer very little information concerning the anatomy and distribution of the inferior phrenic vein (IPV). However, in the last decade, an increasing number of reports have arisen, with reference to the endoscopic embolization of esophageal and paraesophageal varices, as well as venous drainage of hepatocellular carcinomas (HCC). The IPV is one of the major sources of collateral venous drainage in portal hypertension and HCC. The aim of this study was to identify the origin and distribution of the IPVs (right and left), both in normal and (selective) pathological cases. We have examined 300 formalin-fixed adult cadavers, without any visible gastrointestinal disease, and 30 cadavers derived from patients with HCC. The right IPV drained into the following: the inferior vena cava (IVC) inferior to the diaphragm in 90%, the right hepatic vein in 8%, and the IVC superior to the diaphragm in 2%. The left IPV drained into the following: the IVC inferior to the diaphragm in 37%, the left suprarenal vein in 25%, the left renal vein in 15%, the left hepatic vein in 14%, and both the IVC and the left adrenal vein in 1% of the specimens. The IPVs possessed four notable tributaries: anterior, esophageal, lateral and medial. The right IPV served as one of the major extrahepatic draining veins for all 30 cases of HCC. These findings could have potential clinical implications in the transcatheter embolization of esophageal and paraesophageal varices, as well as in mobilizing the supradiaphragmatic segment of IVC.

Adrenal Glands↗

Clinical and morphological diagnosis of cardiac AL amyloidosis: a review of findings and difficulties as illustrated in one case.

BACKGROUND: Primary amyloid light-chain (AL) amyloidosis results from plasma cell dyscrasia. Fibrillar deposits of monoclonal immunoglobulin light chains are present in various organs, especially in the heart. The patients suffer from fatal cardiac dysfunction. CASE REPORT: We report the case of a 54-year-old man with symptoms of cardiac arrhythmia which was refractory to conventional treatment and ablations. At a later stage of his disease, the diagnosis of AL amyloidosis associated with monoclonal gammapathy of uncertain significance was established. Echocardiography, electrocardiography, serum immunofixation studies, abdominal fat aspirate biopsy, and bone marrow biopsy indirectly confirmed the diagnosis of cardiac amyloidosis. The patient died. CONCLUSIONS: The diagnosis of AL cardiac amyloidosis is difficult, the prognosis always serious, the available therapy limited, and the mortality high.

Amyloidosis↗

Utilization of drug-eluting stents in the Veterans Health Administration.

Little is known about how drug-eluting stents (DESs) are used and perform in everyday clinical practice. This report identifies factors associated with the use of DESs in the Veterans Health Administration and compares mortality and the need for coronary artery bypass graft surgery in patients who received DESs or bare metal stents. There was rapid adoption of DESs from the end of 2002 to September 2004, when 52% of percutaneous coronary interventions used DESs. Ten-day death rates in DES and bare metal stent groups were similar (0.8% vs 1.1%), as were 10-day bypass surgery rates (0.2% vs 0.4%). In summary, in a large health care system, DESs were used widely with low rates of death and bypass surgery.

Aged↗

Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype.

PURPOSE: To investigate the proportion of breast cancers arising in patients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients. EXPERIMENTAL DESIGN: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin. RESULTS: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls. CONCLUSION: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.

Biomarkers, Tumor↗

Clinical anatomy of the inferior phrenic artery.

The majority of anatomical textbooks of gross anatomy offer very little information concerning the anatomy and distribution of the inferior phrenic artery (IPA). In the last decade, however, increased numbers of reports have appeared with reference to the arterial supply of hepatocellular carcinoma (HCC). The IPA is a major source of collateral or parasitized arterial supply to this type of carcinoma, second only to the hepatic artery. The aim of this study was to identify the origin and distribution of the IPA (right and left), in normal and pathological cases, and to apply such findings to the clinical scenario of treating hepatic cancer. We have examined 300 formalin-fixed adult cadavers lacking abdominal pathology, and 30 cadavers derived from patients with HCC. Dissections in normal cadavers showed that the right IPA originated from the: a) celiac trunk in 40% of the specimens; b) aorta in 38%; c) renal in 17%; d) left gastric in 3%; and e) hepatic artery proper in 2% of the specimens. The left IPA originated from the: a) celiac trunk in 47%; b) aorta in 45%; c) renal in 5%; d) left gastric in 2%; and e) hepatic artery proper in 1% of the specimens. The IPA gave rise to eight notable branches: ascending, descending, inferior vena cava, superior suprarenal, middle suprarenal, esophageal, diaphragmatic hiatal, and accessory splenic. The right IPA was always associated with HCC and served as the major collateral artery adjunct to the hepatic artery. These findings could have major implications in the transcatheter embolization of HCC patients.

Adrenal Glands↗

A comparison of bilateral breast cancers in BRCA carriers.

BACKGROUND: Women with breast cancer and a BRCA mutation have a high risk of developing a contralateral breast cancer. It is generally believed that the two cancers represent independent events. However, the extent of concordance between the first and second tumors with respect to hormone receptor expression and other pathologic features is unknown. PURPOSE: To determine the degree of concordance of estrogen receptor (ER) status, tumor grade, and histology in tumors from women with bilateral breast cancer and a BRCA mutation. SUBJECTS AND METHODS: Women with a history of bilateral invasive breast cancers were selected from an international registry of women with BRCA1 or BRCA2 mutations. Medical records were reviewed to document the characteristics of each cancer and the treatments received. RESULTS: Data were available for 286 women with bilateral breast cancer and a BRCA mutation (211 BRCA1; 75 BRCA2). The mean interval between first and second tumor was 5.1 years. The two tumors were concordant more often than expected for ER status (P < 0.0001) and for grade (P < 0.0001), but not for histology (P = 0.55). The ER status of the first tumor was highly predictive of the ER status of the second tumor (odds ratio, 8.7; 95% confidence interval, 3.5-21.5; P < 0.0001). Neither age, menopausal status, oophorectomy nor tamoxifen use was predictive of the ER status of the second tumor. CONCLUSIONS: There is strong concordance in ER status and tumor grade between independent primary breast tumors in women with a BRCA mutation. The excess concordance may be due to common risk factors, genetic variation, or the existence of a preneoplastic lesion that is common to both tumors.

Adult↗