Excisional Breast Biopsy Research Articles

Comparative study of the histopathologic changes within and around fibroadenomas

Objective: Fibroadenoma is the most common benign breast tumor but there are a few studies in the literature that describe the histological features of inner and adjacent tissues of fibroadenomas. The aim of the present study is to examine the histological features of the epithelial and stromal tissues within and around fibroadenomas. Materials and Metods: In this study, 52 patients with histopathologically diagnosed fibroadenoma from excisional breast biopsy were retrospectively screened and all hematoxylin eosin stained slides were reevaluated by two pathologists. All data were analyzed with SPSS v.21.0 software package. Results: A statistically significant correlation was detected between complex fibroadenoma and usual ductal hyperplasia (p <0.001), usual ductal hyperplasia was present in 55.9 % of the complex fibroadenomas. No significant association was detected between presence of usual ductal hyperplasia in the surrounding parenchyma and fibroadenoma (p= 0.132). In 26.3 % of fibroadenomas containing usual ductal hyperplasia, usual ductal hyperplasia was present in the adjacent breast parenchyma. There was no significant correlation between complex fibroadenoma and usual ductal hyperplasia or fibrocystic changes in the surrounding parenchyma (p= 0.438 and p= 0.523, respectively). Conclusion: The rates of the proliferative changes that create a risk for breast cancer in and around the fibroadenoma in the younger ages were found similar with the older ages. The examination of the complex and proliferative changes in the fibroadenoma and the proliferative changes in the surrounding breast parenchyma meticulously and specification of all those changes in the report will allow determination of the risk for development of breast cancer more accurately.

An Educational Intervention Reduces Opioids Prescribed Following General Surgery Procedures

BackgroundVariability exists in opioid prescribing practices among surgeons, frequently resulting in the prescription of excessive opioids. This study evaluated the ability of a single educational intervention targeted toward general surgery residents to reduce the quantity of postoperative opioids prescribed. Materials and methodsThis retrospective cohort study evaluated opioid prescribing practices 12 mo prior to and 6 mo following a 30-min lecture for general surgery residents that discussed prescribing guidelines and multimodal analgesia. Opioid volumes (normalized to oral morphine equivalents, OME), opioid type, nonopioid pain medications, and refills requested were analyzed for opioid-naïve adult patients undergoing excisional breast biopsy (EB), mastectomy (M), laparoscopic appendectomy (LA), laparoscopic cholecystectomy (LC), open umbilical hernia repair (OUHR), open inguinal hernia repair (OIHR), or laparoscopic inguinal hernia repair (LIHR). Results695 and 376 patients preintervention and postintervention were included, respectively. Median OME prescribed decreased for EB (150 mg to 75 mg, P < 0.001), M (225 mg to 150 mg, P = 0.85), LA (150 mg to 94 mg, P < 0.001), LC (150 mg to 82 mg, P < 0.001), OUHR (150 mg to 103 mg, P < 0.001), OIHR (175 mg to 100 mg, P = 0.001), and LIHR (200 mg to 113 mg, P < 0.001). Fewer patients received opioids alone and more patients received an opioid with two nonopioid adjuncts (P < 0.001). More patients received oxycodone as fewer received acetaminophen-containing opioid combinations (P < 0.001). Patients requiring refills decreased (11.9% to 7.2%) (P = 0.014). ConclusionsFollowing this targeted intervention, patients were discharged with fewer OME and more nonopioid analgesics, even as refill requests decreased. Educating residents on opioid prescription guidelines and multimodal therapy is effective and should be part of the annual didactic curriculum.

Ultrasound Guided Biopsy in Suspicious Nonpalpable Breast Masses with Histopathological Correlation

Purpose: to evaluate the accuracy of ultra sound guided tru –cut biopsy in non palbable suspicious breast lesions and correlate with pathological results. Introduction: Tru-cut biopsy may be a exact elective will fine needle desire cytology (FNAC) in the finding for breast lesions for a helter skelter symptomatic exactness Similarly as it supplies sufficient tissue to pathologists to create a right histological appraisal. Currently it is those main favored methodology for the finding about breast lesions former should operation rendering should its low cost, secondary accuracy, negligible complications, safe and short duration of the time system. Additionally it might save a considerable measure about liabilities Also unnecessary surgical methods likewise lessens the affinity of muddled surgical methods Also minimizes tolerant anxiety with considerate lesions. Done patients for threatening lesions, What's more should Hosting symptomatic significance, TCB additionally gives sufficient tissue for the assessment from claiming atomic markers which need amazing restorative esteem. Patients and methods: This prospective, controlled ponder selected 40 female patients with non-palpable breast massenet undergone ultimo heartless guided biopsy (USGB) What's more excisional breast biopsy. Post-operative obsessive examination of the example required been directed to guarantee precision for tru-cut biopsy. Results: Special case patient of the instances required false negative outcome about tru-cut biopsy in examination for post-operative excisional biopsy. Conclusion:Ultimo heartless guided biopsy (USGB) may be vital done finding suspicious non palbable breast massenet that guarantee secondary precision outcomes.

Defining the Intrinsic Cardiac Risks of Operations to Improve Preoperative Cardiac Risk Assessments.

Current preoperative cardiac risk stratification practices group operations into broad categories, which might inadequately consider the intrinsic cardiac risks of individual operations. We sought to define the intrinsic cardiac risks of individual operations and to demonstrate how grouping operations might lead to imprecise estimates of perioperative cardiac risk. Elective operations (based on Common Procedural Terminology codes) performed from January 1, 2010 to December 31, 2015 at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program were studied. A composite measure of perioperative adverse cardiac events was defined as either cardiac arrest requiring cardiopulmonary resuscitation or acute myocardial infarction. Operations' intrinsic cardiac risks were derived from mixed-effects models while controlling for patient mix. Resultant risks were sorted into low-, intermediate-, and high-risk categories, and the most commonly performed operations within each category were identified. Intrinsic operative risks were also examined using a representative grouping of operations to portray within-group variation. Sixty-six low, 30 intermediate, and 106 high intrinsic cardiac risk operations were identified. Excisional breast biopsy had the lowest intrinsic cardiac risk (overall rate, 0.01%; odds ratio, 0.11; 95% CI, 0.02 to 0.25) relative to the average, whereas aorto-bifemoral bypass grafting had the highest (overall rate, 4.1%; odds ratio, 6.61; 95% CI, 5.54 to 7.90). There was wide variation in the intrinsic cardiac risks of operations within the representative grouping (median odds ratio, 1.40; interquartile range, 0.88 to 2.17). A continuum of intrinsic cardiac risk exists among operations. Grouping operations into broad categories inadequately accounts for the intrinsic cardiac risk of individual operations.

Outcome of open excisional breast biopsies in Abakaliki, South-East Nigeria.

Introductionopen excisional breast biopsy is a known modality for treatment of breast lumps especially in developing countries. Other sophisticated methods are available for management of breast lumps in more advanced nations. Our aim in this study was to review the outcome of open excision breast biopsies in our setting with a view to improving patient management.Methodsthis study was conducted at the National Obstetric Fistula Centre, Abakaliki, South East Nigeria among women who had excision breast biopsy between January 2015 and December 2016. Data was analysed using Statistical Package for Social Sciences (SPSS), version 21.Resultsa total of 107 case folders were reviewed in this study. The mean age of the women was 27 ± 10 years. Overlying breast incision was the preferred route in 78(72.9%), periareolar incision in 28(26.2%), and Gillard Thomas's method (infero-lateral submammary sulcus incision) used in one patient with bilateral multiple breast lumps (0.9%). The complications recorded in this study were haematoma in 3(2.8%), wound infection in 5(4.7%) and wound breakdown in 1(0.9%). Hypertrophic scar was found in 2(1.8%) patients at follow-up. Overall, most patients were satisfied with the aesthetic outcome of their surgery.Conclusionopen excision breast biopsy is a useful modality for management of breast diseases in our setting. Complication rates are minimal. Both overlying and periareolar breast incisions results in aesthetically satisfactory scar in our practice. Inferior-lateral sub mammary sulcus skin incision is useful when the lumps are multiple and located at different quadrants of the breast. Appropriate use of drain helps to reduce the incidence of haematoma.

Localization Methods for Excisional Biopsy in Women With Nonpalpable Mammographic Abnormalities

IntroductionWith the advent and proliferation of breast cancer screening programs, more women are being diagnosed with mammographic abnormalities that require tissue diagnosis. If imaged-guided biopsy is not possible or previous image-guided biopsies reveal pathologies that require more extensive surgery, guided excisional biopsy/lumpectomy may be necessary. MethodsFifteen women were enrolled in the study of the feasibility of off-site or day-before wire-localization excisional biopsy of the breast with mammographic abnormalities. Five patients had their localization wire placed the day before, whereas 10 patients had their localization the same day with surgery in a distant procedure room under straight local anesthesia. ResultsTwo of the 15 patients had an eventual cancer diagnosis from their wire-localized excisional breast biopsy. All patients had their mammographic abnormality removed with the previously placed core biopsy clip, and there was 100% radiologic/clinical correlation. All patients' wounds healed primarily without any surgical site infections. ConclusionThe protocol answers 2 questions concerning the wire-localized excisional breast biopsy technique. The series shows that the wire-localization technique can be performed the night before or in a location away from the procedure room that would allow better synchronization with surgical schedules or allow the procedure to take place in low-cost settings away from the expense of the hospital operating room.

Complex fibroadenoma and breast cancer risk: a Mayo Clinic Benign Breast Disease Cohort Study.

The purpose of this study is to examine the breast cancer risk overall among women with simple fibroadenoma or complex fibroadenoma and to examine the association of complex fibroadenoma with breast cancer through stratification of other breast cancer risks. The study included women aged 18-85 years from the Mayo Clinic Benign Breast Disease Cohort who underwent excisional breast biopsy from 1967 through 1991. Within this cohort, women who had fibroadenoma were compared to women who did not have fibroadenoma. Breast cancer risk (observed versus expected) across fibroadenoma levels was assessed through standardized incidence ratios (SIRs) by using age- and calendar-stratified incidence rates from the Iowa Surveillance, Epidemiology, and End Results registry. Analyses were performed overall, within subgroups of involution status, with other demographic characteristics (age, year of biopsy, indication for biopsy, and family history), and with histologic characteristics, including overall impression [nonproliferative disease, proliferative disease without atypia (PDWA), or atypical hyperplasia]. Fibroadenoma was identified in 2136 women [noncomplex, 1835 (85.9%); complex, 301 (14.1%)]. SIR for noncomplex fibroadenoma was 1.49 (95% CI 1.26-1.74); for complex fibroadenoma, it was 2.27 (95% CI 1.63-3.10) (test for heterogeneity in SIR, P = .02). However, women with complex fibroadenoma were more likely to have other, concomitant high-risk histologic characteristics (e.g., incomplete involution and PDWA). In analyses stratified by involution status and PDWA, complex fibroadenoma was not an independent risk marker for breast cancer. Complex fibroadenoma does not confer increased breast cancer risk beyond other established histologic characteristics.

Flat epithelial atypia and risk of breast cancer: A Mayo cohort study.

Based on its cytologic features, and its co-occurrence with atypical hyperplasia and breast cancer, flat epithelial atypia (FEA) has been proposed as a precursor lesion on the pathway to the development of breast cancer. It is often referred to as an "atypical" or high-risk lesion. However, to the authors' knowledge, the long-term risk of breast cancer in women with FEA is undefined. Specimens with FEA were identified among excisional breast biopsies in the Mayo Clinic Benign Breast Disease Cohort, which includes 11,591 women who had benign biopsy findings at the Mayo Clinic in Rochester, Minnesota between 1967 and 2001. Breast cancer risk among subsets of patients with FEA and nonproliferative, proliferative, and atypical hyperplasia (AH) was assessed using standardized incidence ratios (SIRs) compared with the Iowa Surveillance, Epidemiology, and End Results registry. FEA was identified in 282 women (2.4%); 130 had associated AH (46%) and 152 (54%) were classified as having proliferative disease without atypia (PDWA). With median follow-up of 16.8 years, the SIR for breast cancer in patients with AH plus FEA was 4.74 (95% confidence interval [95% CI], 3.17-6.81) versus 4.23 (95% CI, 3.44-5.13) for those with AH without FEA (P = .59). The SIR for patients with PDWA plus FEA was 2.04 (95% CI, 1.23-3.19) versus 1.90 (95% CI, 1.72-2.09) for patients with PDWA without FEA (P = .76). FEA is an uncommon finding in women with benign breast disease. FEA does not appear to convey an independent risk of breast cancer beyond that of the associated PDWA or AH.

Burkitt's lymphoma of the breast metastatic to the ovary diagnosed during pregnancy

In September 2010, a 30-year-old primigravida at 16 weeks of gestation was referred to our institution because of rapid and progressive bilateral enlargement of her breasts. Physical examination disclosed enlarged, grossly indurated breasts with tightness of the skin (Figure 1a) and no peripheral adenopathy. Ultrasound examination of the breasts revealed increased glandular vascularization and diffuse parenchymal disease without focal masses (Figure 2). Transvaginal sonography showed bilateral ovoidal solid ovarian masses, 7 cm (right) and 6.4 cm (left) in size, with homogeneous hypoechoic echostructure and regular margins (Figure 1b). On color Doppler examination, rich vascularization was detected; in particular, a main tree-shaped vessel corresponding to the so-called ‘lead vessel’, described in the literature as strongly predictive of metastatic ovarian tumor, was observed1 (Figure 3). No ascites was documented. The sonographic characteristics prompted us to suspect the presence of metastatic disease of the ovary from a primary unknown tumor. Excisional biopsy of the left breast and biopsies of both ovarian masses were performed. Laparoscopic examination confirmed the ultrasound findings and was negative for abdominal carcinomatosis. Both morphological and immunophenotypic characteristics of breast and ovarian biopsies were indicative of Burkitt's lymphoma. Bone marrow examinations were negative. The patient's clinical condition rapidly deteriorated, and it was felt that prompt treatment was essential. After careful counseling on disease prognosis and fetal risks related to the cytotoxic treatment, chemotherapy was initiated according to a treatment protocol known as the Magrath protocol, which consists of alternating cycles of intensive chemotherapy, but with intravenous and intrathecal methotrexate omitted2. On day 40 after the start of treatment and at a gestational age of 22 weeks, fetal heart beats and movements were no longer detected, and spontaneous delivery ensued. One week after dilatation and curettage of the uterine cavity, anti-lymphoma therapy was resumed, including methotrexate and the CD20 monoclonal antibody, rituximab. A whole-body computed tomography scan revealed complete radiological response on day 106. On clinical examination after the end of therapy, both breasts appeared to be of normal dimensions and morphology (Figure 1c) and transvaginal ultrasound examination revealed ovaries of normal size and regular echostructure (Figure 1d). At 31 months from diagnosis, the patient remained disease free. Burkitt's lymphoma is a highly aggressive malignancy that may develop during pregnancy; rare cases of the condition presenting as primary bilateral breast tumors during pregnancy or after (during lactation) have been previously described3, and cases of ovarian location during pregnancy appear to be even more rare4. The rarity and unfavorable clinical behavior of this condition represent a challenge for clinicians because the prognosis of this chemosensitive tumor is strictly dependent on early diagnosis and prompt therapy, which also has to take into account the high risk of fetal loss, particularly during the first trimester5, 6. Although sonography has been the most frequently used diagnostic approach during pregnancy in most published cases4, the sonographic features of ovarian masses have not previously led to the prompt suspicion of metastatic ovarian disease, the diagnosis being made only after definitive pathological examination. Conversely, in our case, the detection of bilateral solid ovarian masses with the typical vascularization of metastatic tumors, namely the ‘lead vessel’6, contributed to the examiner's confidence in making the diagnosis of metastases to the ovary. This experience confirms the role of ultrasound examination in the management of adnexal masses, in particular during pregnancy. Ultrasound also has the advantage of being readily available, quick to perform, inexpensive and widely accepted by patients. A. C. Testa*, I. De Blasis, A. Di Legge, P. Belli S. Hohaus and G. Ferrandina Department of Obstetrics and Gynecology (Gynecologic Oncology Unit), Catholic University of the Sacred Heart, Rome, Italy *Correspondence. (e-mail: atesta@rm.unicatt.it)

Abstract P5-01-08: Complex fibroadenoma is not an independent risk marker for breast cancer

Abstract Background: Fibroadenoma (FA) is a relatively common benign breast tumor that can occur in women of any age, with a peak incidence during the second and third decades. The only previous study of this lesion reported that FAs are associated with a 2.2 times increased risk of developing invasive breast cancer (BC) compared to matched controls [1]. This relative risk may increase to 3.1 among patients with complex FA, and remains elevated for decades after diagnosis. However, this study did not thoroughly account for other forms of concomitant risk factors. Our investigative team sought to examine breast cancer risk among women with non-complex and complex FA, overall and stratified by other BC risk factors. Materials and Methods: The study cohort included women between ages 18 to 85 in the Mayo Benign Breast Disease (BBD) Cohort who underwent excisional breast biopsy between 1967and1991 and were found to have a FA. FA was defined histologically as a combination of epithelial and stromal proliferation. Complex FA was defined as FA associated with any of the following features: sclerosing adenosis, epithelial calcifications, papillary apocrine change, and microcysts greater than 3.0 mm. The primary endpoint was a diagnosis of BC, determined using the Mayo medical record and questionnaire information from study participants. A single breast pathologist, blinded to the initial diagnosis and clinical outcome, performed pathology review. Observed vs. expected BC risk across levels of FA was assessed via standardized incidence ratios (SIRs), using age-stratified incidence rates from the Iowa Surveillance, Epidemiology, and End Results (SEER) registry. Analyses were carried out overall and within subgroups of involution status (none, partial, complete) and overall histology (non-proliferative disease [NP], proliferative disease without atypia [PDWA] or atypical hyperplasia [AH]). Results: Of 9097 women in the Mayo BBD Cohort, FA were identified in 2139- non-complex in 1903 (20.9%) and complex in 236 (2.6%). The greatest proportion of FA occurred in the 40–69 age range. The mean ages for women with non-complex FA and complex FA were 45.7 and 50.2 years respectively. The SIR of breast cancer in the overall BBD cohort was 1.5 (95% CI [1.4–1.6]). The SIR among women with non-complex FA was 1.5 (95% CI [1.3–1.8]), and for complex FA increased to 2.41 (95% CI [1.7–3.4]). However, women with complex FA were more likely to have other concomitant high-risk histologic features such as PDWA and incomplete involution. In stratified analyses accounting for involution status and PDWA, complex FA did not demonstrate an independent increase in BC risk. Conclusion: Complex FA does not confer an increased risk for BC beyond other established histologic features. Therefore, women with complex FA should be managed based upon a risk level consistent with the major histologic category of PDWA and/or AH. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-08.

Diaforodiagnostic dilemma of a breast tumor in a patient with known history of chest sarcoidosis: a diagnostic approach

Abstract Breast sarcoidosis is extremely rare, substantially less frequent than other extrapulmonary manifestations of sarcoidosis. It can mimic a benign or malignant tumor of the breast. We describe the case of a patient with a history of pulmonary sarcoidosis referred to our hospital for a screening mammography. Mammographic findings raised the suspicion for a breast mass. An additional breast ultrasound and fine -needle aspiration biopsy were performed. Finally, patient underwent a excisional biopsy of the left breast and the histopathological report revealed sarcoidosis.

Abstract 2213: The normal breast study: Understanding the normal tissue adjacent to breast cancers. Epithelial-to-Mesenchymal transition (EMT) signatures

Abstract Significance: Breast Cancers (BC) evolve and acquire adaptive changes while in active communication with the surrounding host normal tissue. Understanding how host tissue interacts with cancers during breast cancer progression could lead to novel biomarkers or targeted therapies. Innovation: We hypothesized that novel molecular subtypes of microenvironment (ME) can be identified and have prognostic value. Stromal signatures are poorly understood and the independent prognostic value of stroma and/or ME response has not been widely studied. Approach: We used gene expression data 1) to identify molecular subtypes of microenvironment, 2) to study the distribution and prevalence of microenvironment subtypes in an ethnically diverse group of BC cases and 3) to test the value of ME in predicting breast cancer progression. In 2009, our team initiated the UNC NORMAL BREAST STUDY (NBS), a unique epidemiologic study of normal tissue from ethnically diverse patients at UNC Hospitals. The NBS has recruited over 200 patients undergoing breast surgery at UNC Hospitals, including cosmetic surgeries, excisional diagnostic breast biopsies, lumpectomies and mastectomies. All participants donate snap frozen and paraffin-embedded normal breast tissue. For all patients who have been diagnosed with breast cancer, the gross distance between the tumor and the normal breast tissue specimen is measured. In addition all study participants are asked to submit a blood sample and complete a telephone interview regarding demographics and environmental exposures. Medical record abstraction is performed to obtain treatment data and anthropometry. Each sample is carefully analyzed for histopathology and whole genome gene expression data is collected. Results: Among the breast cancer patients profiled in our initial studies, unsupervised clustering resulted in two groups of patients, one of which showed expression features suggestive of an activated mesenchyme. We then generated an EMT signature using cell line models and observed that this signature is enriched in one cluster or subgroup of these patients. In the approximately 40% of patients where the EMT signature is enriched, survival was decreased, and survival was significantly decreased among patients with ER positive disease. Conclusion: The NBS allows a unique opportunity to make an impact in discovering novel biology of human breast cancer microenvironment. The information gained from this translational study will establish whether microenvironment subtypes are associated with recurrence risk and will elucidate how variation in host biology contributes to BC disparities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2213. doi:10.1158/1538-7445.AM2011-2213

Metastasis to the breast from an adenocarcinoma of the lung with extensive micropapillary component: a case report and review of the literature

Breast metastasis from extra-mammary malignancy is rare. Based on the literature an incidence of 0.4-1.3% is reported. The primary malignancies most commonly metastasizing to the breast are leukemia-lymphoma, and malignant melanoma. We present a case of metastasis to the breast from a pulmonary adenocarcinoma, with extensive micropapillary component, diagnosed concomitantly with the primary tumor. A 73-year-old female presented with dyspnea and dry cough of 4 weeks duration and a massive pleural effusion was found on a chest radiograph. Additionally, on physical examination a poorly defined mass was noted in the upper outer quadrant of the left breast. The patient underwent bronchoscopy, excisional breast biopsy and medical thoracoscopy. By cytology, histology and immunohistochemistry primary lung adenocarcinoma with metastasis to the breast and parietal pleura was diagnosed. Both the primary and metastatic anatomic sites demonstrated histologically extensive micropapillary component, which is recently recognized as an important prognostic factor. The patient received chemotherapy but passed away within 7 months. Accurate differentiation of metastatic from primary carcinoma is of crucial importance because the treatment and prognosis differ significantly.

Are Percutaneous Biopsy Rates a Reasonable Quality Measure in Breast Cancer Management?

Utilization of percutaneous needle biopsy (PNB) has been proposed as a quality measure of breast cancer care. We evaluated rates and reasons for failure of patients undergoing PNB as the initial diagnostic procedure for evaluation of breast pathology. We performed a retrospective review of sequential patients undergoing image-guided PNB and open surgical excisional breast biopsies from January 2006 to July 2009 at our institution. Factors associated with failure to undergo a percutaneous approach were analyzed. During the study period, 1196 breast biopsies were performed; 87 (7.3%) were open surgical biopsies, and 1109 (92.7%) were PNB. Imaging used for percutaneous guidance or needle localization was ultrasound in 58.9%, mammogram in 40.0%, and magnetic resonance imaging (MRI) in 0.9%. Open surgical excisional biopsy was associated with mammographic guidance (P<.001), location in the central or lower inner quadrant of the breast (P=.002), BIRADS score of 1 or 6 (P<.001), or calcifications as target (P<.001). There were no differences in rates of PNB by age, size of lesion, or breast density. Reasons for failure of PNB were technical (calcifications not visualized, proximity to implant, etc.) in 86.2% of cases. No reason was documented in 10.3%, and 3.4% of patients refused a percutaneous approach. The majority of patients in this series underwent PNB as an initial diagnostic approach. Most percutaneous failures are due to technical reasons. PNB rates are a reasonable quality measure in breast cancer care. Documentation of failure to meet this benchmark should be stringently monitored.

Pseudoangiomatous Stromal Hyperplasia and Breast Cancer Risk

Pseudoangiomatous stromal hyperplasia (PASH) is a benign localized fibrotic lesion in which clusters of spindle cells form cleftlike spaces, resembling ectatic vessels. Its relationship to breast cancer risk has not been characterized. Histological presence of PASH was evaluated by review of archival slides in a single institution cohort of women who underwent benign excisional breast biopsy from 1967 to 1991. Relative risks for subsequent breast cancer were estimated using standardized incidence ratios (SIR), comparing the observed number of cancers with those expected based on Iowa SEER data (mean follow-up 18.5 years). PASH was identified in 579 of 9065 biopsies (6.4%). Women with PASH were younger, more likely to have a palpable mass as indication for biopsy, and had less lobular involution compared with those without PASH (all P < 0.001), while they did not differ by family history of breast cancer or degree of epithelial proliferation. Breast cancers occurred in 34 women with PASH (5.9%) and 789 without (8.8%). Women with PASH had lower risk of breast cancer (SIR 1.03, 95% confidence interval [95% CI] 0.71-1.44) than those without PASH (SIR 1.54, 95% CI 1.43-1.65), P = 0.01. Lower levels of breast cancer risk for the PASH group persisted in analyses stratified by age, family history, epithelial proliferation, and involution. The cancers in the PASH group occurred predominantly in the ipsilateral breast more than 5 years after biopsy. Despite clinical concern generated by palpable density often associated with PASH, this relatively uncommon histological finding does not connote increased risk of subsequent breast cancer.

Lobular Involution and Mammographic Density: Independent Contributors to Breast Cancer Risk.

Abstract Background: Women with benign breast disease are at elevated breast cancer risk. In order to accurately predict a woman's individual risk of breast cancer, a breast cancer risk-prediction model is needed that incorporates significant breast cancer risk factors. This report describes two factors: tissue based assessment of lobular involution, and radiological marker- mammographic density (MD). Lobular involution, or physiologic atrophy of the breast glandular epithelium, is inversely associated with breast cancer risk. MD is a strong positive risk factor for breast cancer. With increasing age, the extent of lobular involution increases while MD decreases. However, it is unclear whether involution and MD represent independent breast cancer risk factors. We examined breast cancer risk associated with lobular involution and MD in women with benign breast disease (BBD) to determine whether these features are independently associated with breast cancer risk.Methods: Using the Mayo Clinic Surgical and Pathology Indices, 9376 women ages 18 to 85 with benign excisional breast biopsy between January 1, 1967 and December 31, 1991 were identified and formed the Mayo BBD cohort. We studied a sub-cohort of women diagnosed with BBD between 1985 and 1991 (when MD was clinically assessed and recorded) who had a mammogram within 6 months of the BBD diagnosis. Breast cancer outcomes were determined through the Mayo medical records and a study-specific questionnaire. Lobular involution extent was assessed in background tissue as 'none' (0% lobules involuted), 'partial' (1-74% lobules involuted) or 'complete' (≥75% lobules involuted). MD was classified as Wolfe's parenchymal pattern (PP) as N1/ fatty; P1; P2; and DY/ homogenously dense. Hazard ratios and confidence intervals were calculated using Cox regression analyses, adjusting for confounders: age, parity, BMI, BBD histology, menopausal status, family history, PP and involution extent.Results: A total of 2666 women in the Mayo BBD cohort, with biopsies between 1985 and 1991, had a mammogram within 6 months of the breast biopsy. The mean age at biopsy was 54.6 years. After a mean follow-up of 13.3 years, 172 (6.5%) women developed breast cancer. After adjustment for PP and other confounders, women with no or partial involution had elevated risk compared to women with complete involution (HR 2.62 [95% CI 1.39, 4.94] for no involution and 1.61 [95% CI 1.03, 2.53] for partial involution; complete involution as reference group; p for trend 0.003). Moreover, women with dense breasts were at greater risk compared to women with nondense breasts (HR 1.67 [95% CI 1.0, 2.73] for DY pattern, 1.96 [95% CI 1.2 – 3.21] for P2, 1.23 [95% CI 0.67, 2.26] for P1; N1 category as reference group; p for trend 0.02). Multivariate analyses also showed that women with the combination of no involution and dense breasts had greater risk compared to those with complete involution and nondense breasts (HR 4.08 [95% CI 1.72, 9.68]).Conclusion: Lobular involution and MD are both risk factors for breast cancer; this report is the first to demonstrate that each provides unique information about breast cancer risk. These findings emphasize the potential for inclusion of both these factors in future breast cancer risk-prediction models. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6064.

Optimal Use of Re-Excision in Patients Diagnosed with Early-Stage Breast Cancer by Excisional Biopsy Treated with Breast-Conserving Therapy

The goal of the current study is to help refine guidelines for the need for re-excision and the appropriate amount of breast tissue to re-excise in patients with early breast cancer following excisional breast biopsy when treated with breast-conserving therapy (BCT). The study population consisted of 441 patients derived from a dataset of 607 consecutive cases of stage I and II breast cancer treated with BCT, in which patients underwent primary excisional diagnostic biopsy and subsequent re-excision prior to the initiation of radiation therapy (RT). A single pathologist reviewed all specimens. Re-excision was indicated because tumor was found close to or involving the resection margin. In 333 of the 441 cases, it was possible to measure the extension of carcinoma into the re-excision specimen. Margins were classified as negative (carcinoma>4.2 mm from the margin), near (<4.2 mm from the margin) or positive. Any carcinoma identified near the final margin was quantified by width of invasive carcinoma and number of ductal carcinoma in situ (DCIS) ducts near the margin and subdivided into three distinct groups: least, intermediate, and greatest amount. These factors were then analyzed to determine the likelihood and extent of residual carcinoma in re-excision specimens. Statistical analysis was performed using Systat version 10 (SPSS Inc., Chicago, IL). The quantity of carcinoma near the initial biopsy margin and the invasive carcinoma-to-specimen dimension ratio demonstrated a significant association with increasing amounts of residual carcinoma at re-excision. Combination of these two variables allowed for a statistically significant (P<0.001) calculation of risk index for identifying significant residual invasive carcinoma or DCIS in the adjacent breast parenchyma at re-excision, and yielded stratification into low- (6%), intermediate- (27%), and high-risk (44%) groups. In re-excision specimens, the observed distance of carcinoma extension into adjacent breast tissue was associated with a statistically significant decrease in the ratio of the initial excisional biopsy specimen dimensions and invasive carcinoma dimensions. Combining the initial margin status with the specimen-to-invasive carcinoma maximum dimension ratio yielded an accurate predictor of the maximum distance of tumor extension. Evaluation of the initial excisional biopsy margin status in correlation with the invasive carcinoma-to-specimen maximum dimension ratio may be helpful for (1) identifying patients who require re-excision prior to RT and (2) predicting the quantity of additional breast tissue to excise to ensure adequate surgical margins with BCT.

Generalized essential telangiectasia with predilection for surgical scar

To the Editor: A 79-year-old female presented to our clinic for an annual skin examination. Her medical history was notable for multiple surgeries, including wide excision of melanoma of the mid-back, appendectomy, hysterectomy, open cholecystectomy, and excisional breast biopsy.

Benign breast disease and breast cancer risk in young women.

Abstract Abstract #62 Background: Breast cancer is the leading cause of cancer deaths in younger women (25 to 49 years of age). Young women with breast cancer also have worse overall survival and increased risk of recurrence compared to older women with breast cancer. Innovative approaches to understanding risk factors and tissue characteristics for the younger population can improve understanding of breast cancer etiology and enhance risk-stratification for these women. This study was aimed at examining breast cancer risk factors among young women (&amp;lt;50 years) with BBD. Materials and Methods: Utilizing the Mayo Clinic Surgical and Pathology Indices, women ages 18 to 85 who had benign excisional breast biopsy between January 1, 1967 and December 31, 1991 were identified. The diagnosis of breast cancer served as the study endpoint and was determined using the Mayo medical record and questionnaire information from study participants. The breast pathologist, blinded to the initial diagnosis and clinical outcome, performed pathology review. BBD was classified as non-proliferative disease (NPD), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH). Age-related lobular involution (reduction in number and size of acini per lobule) was classified as none-0%, partial- 1 to74%, or complete- &amp;gt;75% involution. Relative risk (RR) was estimated by comparing the number of observed breast cancers with the number expected, based on breast cancer rates in the Iowa Surveillance, Epidemiology, and End Results registry. Results: Of the 9376 women in the Mayo BBD cohort, 4460 women were aged &amp;lt;50 years at BBD diagnosis and formed the study cohort. The mean age at BBD diagnosis was 39.4 (+ 8.3) years. With a median follow-up of 20 years, 326 breast cancer cases were identified. The histologic findings were NPD in 72% of women, PDWA in 26%, and AH in 2%. The relative risk of breast cancer for the overall cohort of young women with BBD was 1.5 (95% CI [1.4, 1.7]). The relative risk among those with AH was 6.9 (95% CI [4.6, 10.1), compared with a RR of 2.0 (95% CI [1.7, 2.4]) for PDWA, and RR of 1.2 (95% CI [1.0, 1.4]) for NPD. Risk was associated with extent of lobular involution (RR for no involution was 1.7 (95%CI [1.4, 2.1]); partial involution 1.4 (95%CI [1.2, 1.7]); complete involution 0.7 (95%CI [0.3, 1.4]). Family history was available for 83% of the cohort and RR was 2.2 (95% CI [1.7, 2.8]) for women with strong family history and was 1.3 (95% CI [1.1, 1.6]) for women with no family history. Discussion: Young women with BBD are at increased risk of breast cancer. Risk is high in women with atypical hyperplasia, and those with a family history of breast cancer. Lobular involution is associated with reduced breast cancer risk in this population, suggesting a role in modifying breast cancer risk. These findings suggest the need for further research in this population, along with tissue-based studies to examine the processes leading to breast cancer, and enable identification of those women at highest risk. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 62.

Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target

FoxP3 is a marker for immunosuppressive CD25+CD4+ regulatory T cells. These regulatory T cells are thought to play a role in inducing immune tolerance to antigens and may be selectively recruited by carcinomas. We investigated whether breast carcinomas had significant numbers of FoxP3-positive regulatory T cells by immunohistochemistry, and if their presence was associated with other prognostic factors, such as Nottingham grade, hormone receptor immunohistochemical profile, tumor size, or lymph node metastases. Ninety-seven needle core or excisional breast biopsies with invasive breast carcinoma diagnosed at the University of Washington were stained with antibodies to FoxP3, estrogen receptor, and Her2/neu. The numbers of FoxP3-positive cells present within the neoplastic epithelium, and immediately adjacent stroma were counted manually in three high-powered fields (HPFs; × 400) by two independent pathologists. The average scores were then correlated with the parameters of interest. A threshold of ≥15 FoxP3-positive cells/HPF was used to define a FoxP3-positive case in some analyses. Higher average numbers of FoxP3-positive cells present significantly correlated with higher Nottingham grade status (P=0.000229). In addition, the presence of significant numbers (≥15/HPF) of FoxP3-positive cells in breast carcinoma was positively associated with higher Nottingham grade (P=0.00002585). Higher average numbers of FoxP3-positive cells were also significantly associated with larger tumor size (>2.0 cm; P=0.012824) and trended toward an association with estrogen receptor negativity. Interestingly, ‘triple-negative’ (estrogen and progesterone receptor negative and Her2/neu negative) Nottingham grade III cases were also significantly associated with high numbers of FoxP3 cells. These results argue that regulatory T cells may play a role in inducing immune tolerance to higher grade, more aggressive breast carcinomas, and are a potential therapeutic target for these cancers.