Carol Reynolds

Mayo Foundation for Medical Education and Research, Rochester, MI, United States

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Publications (79)413.74 Total impact

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    ABSTRACT: OBJECTIVE. The purpose of this study was to determine the proportion of invasive lobular carcinomas with increased sonographic echogenicity. MATERIALS AND METHODS. A retrospective review of mammographic and sonographic findings included cases of pure invasive lobular carcinoma with available images from January 1998 to June 2010. We assessed ultrasound images for the presence of a mass, internal echogenicity, margin characteristics, and attenuation effects. In hyperechoic tumors, more than 90% of the mass had increased echogenicity compared with surrounding fat. In heterogeneously echogenic tumors, the echogenic component constituted 20-90% of the tumor. Findings at mammography, MRI, and surgery were correlated with sonographic findings. A breast pathologist reviewed histologic findings and confirmed the diagnosis of pure invasive lobular carcinoma. RESULTS. Of 509 invasive lobular carcinomas, 27 (5%) were hyperechoic, of which 13 (48%) were associated with posterior acoustic shadowing. Heterogeneously echogenic cancer was seen in 57 (11%) cases. The most common sonographic finding was a hypoechoic, irregular mass with or without posterior shadowing (n = 323; 63%). In 66 (13%) lesions, focal shadowing was seen without a discrete mass. Fourteen (3%) lesions were isoechoic with respect to surrounding normal adipose tissue without acoustic shadowing. Twenty-two (4%) of the malignant tumors were not identified sonographically. Of these, 15 (68%) had mammographic abnormalities, one (5%) was seen at MRI, and six (27%) presented as palpable masses that were surgically excised. CONCLUSION. Pure invasive lobular carcinomas can present as a hyperechoic mass or with substantial hyperechoic component. All sonographic lesion characteristics should be evaluated and biopsy recommended when there are suspicious features, even in a lesion that is predominantly hyperechoic.
    American Journal of Roentgenology 11/2013; 201(5):W765-9. · 2.90 Impact Factor
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    ABSTRACT: ACOSOG Z11 and other studies showing little benefit to axillary dissection (ALND) for early-stage breast cancers with limited nodal disease have led to questioning the value of preoperative axillary imaging ± ultrasound-guided needle biopsy (USNB). Data are lacking on the value of this approach in identifying cases that fall outside Z11 guidelines. We studied 988 consecutive patients with invasive breast cancers who underwent operation including axillary surgery in 2010-2011. Preoperative axillary ultrasonography (AUS) was performed in 92% and breast/axillary magnetic resonance imaging (MRI) in 51%; 82 (33.5%) of 245 patients with suspicious lymph nodes (LN) were USNB-positive. Regarding nodal status, AUS, MRI, and USNB had negative and positive predictive values of 78%, 76%, 70% and 54%, 58%, 100%, respectively. AUS/MRI visualization of one versus multiple abnormal LNs visualized predicted >2LN+ on final pathology (13.5%/15.1% % vs 30.8%/32.6%, P < .009). Among USNB-LN+ T1/T2 patients, 51.6% had 1-2 LN+ while 60% with multiple and 31% with one AUS-abnormal LN(s) had > 2LN+, P = .001. In our contemporary series, preoperative AUS±USNB streamlined surgical care for 29% of node-positive patients. Two-thirds of T1/T2 USNB-LN+ patients with multiple AUS-suspicious LNs had >2LN+, suggesting they should undergo ALND without SLNB. AUS±USNB helps identify node-positive breast cancer patients who fall outside Z11 guidelines.
    Surgery 10/2013; 154(4):831-40. · 3.37 Impact Factor
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    ABSTRACT: The purpose of this article is to present imaging findings of invasive ductal carcinoma with micropapillary features with clinical and pathologic correlation. We retrospectively searched our institution's surgical pathology database for patients with pathologically proven invasive ductal carcinoma with micropapillary features. Forty-one patients with images available for review were included in the study. Mammographic, sonographic, and MRI findings were assessed using the American College of Radiology's BI-RADS lexicon. Molecular breast imaging findings were reviewed using a molecular breast imaging lexicon. Imaging findings were correlated with clinical presentation and pathologic findings. Mammographically, the most common finding was an irregular spiculated mass. Sonographically, the most common finding was an irregular hypoechoic mass with spiculated margins and posterior acoustic shadowing. With MRI, the most common finding was an irregular mass with washout kinetics, but we also observed diffuse heterogeneous nonmasslike enhancement throughout the breast. Molecular breast imaging was available for one patient and showed multicentric radiotracer uptake. Analysis of 39 pathologic specimens showed 27 (69%) with angiolymphatic invasion. Axillary nodal metastases were present in 23 patients (59%), nine (23%) with extranodal extension. The imaging features of invasive ductal carcinoma of the breast with micropapillary features typically were highly suggestive of malignancy. The malignancies were strongly associated with lymphovascular invasion and lymph node metastases. Radiologists should be aware of the imaging features of this unusual variant and should consider axillary sonography if this entity is found in a core needle biopsy specimen.
    American Journal of Roentgenology 03/2013; 200(3):689-95. · 2.90 Impact Factor
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    ABSTRACT: BACKGROUND: The purpose of this study was to determine whether surgical excision of benign solitary intraductal papillomas (BSIP) diagnosed by core needle biopsy (CNBx) without an associated high-risk lesion and concordant with imaging is justified. METHODS: A review of all papillary lesions diagnosed by CNBx from January 2003 to June 2010 was performed. Available histologic and radiologic materials were evaluated in a blinded fashion by three pathologists and three dedicated breast radiologists, respectively, to assess for concordance. The papillary lesions were designated as benign, atypical, or malignant. There were 16 BSIPs excluded because of an adjacent high-risk lesion or same-quadrant ipsilateral cancer. All immediate and delayed excisional specimens were reviewed. Clinical and radiologic data were recorded. RESULTS: A total of 299 papillary lesions diagnosed on CNBx and concordant with imaging were identified. Of these, 240 (80 %) were classified as benign, 49 (16 %) atypical, and 10 (3 %) malignant. After exclusions, 77 of 224 women in our study cohort (34 %) underwent surgical excision with no atypical or malignant upgrades. Of the remaining 147 women diagnosed with a BSIP on CNBx, 47 (32 %) were lost to follow-up and 100 (68 %) were observed. All 100 observed patients had stable imaging findings at follow-up (4.8-93.8 months, mean 36.0 months). CONCLUSIONS: The likelihood of diagnosing atypia or malignancy after surgical excision of a BSIP diagnosed on CNBx without associated high-risk lesion or ipsilateral quadrant malignancy is extremely low. For this distinct subset of patients with a BSIP, these data justify close imaging follow-up, rather than surgical excision.
    Annals of Surgical Oncology 01/2013; · 4.12 Impact Factor
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    ABSTRACT: Background: Controversy exists regarding CYP2D6 genotype and tamoxifen efficacy. Methods: A matched case-control study was conducted utilizing the Austrian Breast and Colorectal Cancer Study Group Trial 8 that randomized post-menopausal women with estrogen receptor positive breast cancer to tamoxifen for 5 years (Arm A) or tamoxifen for 2 years followed by anastrozole for 3 years (Arm B). Cases had disease recurrence, contralateral breast cancer, second non-breast cancer, or died. For each case, controls were identified from the same treatment arm of similar age, surgery/radiation, and TNM stage. Genotyping was performed for alleles associated with no (PM; *3, *4, *6); reduced (IM; *10, and *41); and extensive (EM: absence of these alleles) CYP2D6 metabolism. Findings: The common CYP2D6 *4 allele was in Hardy Weinberg Equilibrium. In Arm A during the first 5 years of therapy, women with 2 poor alleles (PM/PM: OR=2.45, 95% CI: 1.05-5.73, p=0.04) and women with one poor allele (PM/IM or PM/EM: OR=1.67, 95% CI: 0.95-2.93, p=0.07) had a higher likelihood of an event than women with two extensive alleles (EM/EM). In years 3-5 when patients remained on tamoxifen (Arm A) or switched to anastrozole (Arm B), PM/PM tended towards a higher likelihood of a disease event relative to EM/EM (OR= 2.40, 95% CI: 0.86-6.66, p=0.09) among women on Arm A but not among women on Arm B (OR= 0.28; 95% CI: 0.03-2.30). CONCLUSION: In ABCSG8, the negative effects of reduced CYP2D6 metabolism were observed only during the period of tamoxifen administration, and not after switching to anastrozole.
    Clinical Cancer Research 12/2012; · 7.84 Impact Factor
  • Clinical Cancer Research 12/2012; · 7.84 Impact Factor
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    ABSTRACT: Radioactive seed localization (RSL) is an increasingly utilized and effective approach to surgical excision of radiographically identified lesions in the breast. This approach has been reported to be at least as convenient to the patient, radiologist, and surgeon as the standard wire localized approach but with the considerable added benefit of a lower positive margin rate in some studies. To date, there is little information in the published medical literature concerning the optimal handling of these specimens in the pathology laboratory. The US Nuclear Regulatory Commission and its Agreement States oversee the use of radioactive materials in clinical practice and provide guidelines for the performance of RSL procedures, including the safe handling of radioactive seeds. The RSL procedure involves multiple departments, and a robust process should be in place to ensure appropriate accountability, seed tracking, and minimal radiation exposure to staff. This article describes how to properly and safely handle RSL breast specimens, including regulation requirements, specimen labeling and receipt, specimen dissection, protective wear, and seed retrieval, transport, and disposal.
    The American journal of surgical pathology 10/2012; 36(11):1718-23. · 4.06 Impact Factor
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    ABSTRACT: Amyloidosis is a disorder characterized by extracellular deposition of proteins in an abnormal fibrillar configuration. Amyloidosis can be localized or systemic and may affect any organ. Breast involvement by amyloidosis has rarely been reported. In this study, we described the characteristics of 40 cases of breast amyloidosis that were reviewed at the Division of Anatomic Pathology at Mayo Clinic from 1995 to 2011. The cohort included 39 women and 1 man with a mean age of 60 years. The type of amyloidosis, determined by immunohistochemistry or mass spectrometry-based proteomics in 26 patients, was immunoglobulin-associated in all cases (AL-kappa type in 15 (58%) cases, AL-lambda in 10 (38%) and mixed heavy and light chains (AH/AL) in 1 (4%) case). Mass spectrometry-based proteomics was able to determine the type of amyloidosis in 95% of cases tested compared with 69% of cases by immunohistochemistry. In addition to amyloidosis, the breast biopsy showed a hematologic disorder in 55% of cases, most commonly MALT lymphoma. One patient had concurrent intraductal carcinoma, but none had invasive carcinoma. Of the 15 patients seen in our institution, 53% had localized amyloidosis and 47% had extramammary amyloid involvement, which was diagnosed before breast amyloidosis in most patients. M-spike was detected in the blood in 62%. After a median follow-up of 33.5 months in 12 patients, 5 died, mostly of complications of lymphoma or leukemia. In conclusion, our findings indicate that breast amyloidosis is of the AL type in the vast majority of patients (usually kappa). It is associated with systemic amyloidosis in close to half of patients and with hematologic malignancy in the breast in over half of patients. Therefore, further work up to rule out hematologic malignancy and/or systemic amyloidosis is recommended. Mass spectrometry-based proteomics is superior to immunohistochemistry for typing of breast amyloidosis.Modern Pathology advance online publication, 28 September 2012; doi:10.1038/modpathol.2012.167.
    Modern Pathology 09/2012; · 5.25 Impact Factor
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    ABSTRACT: Lobular neoplasia (LN) includes atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS). LN often is an incidental finding on breast core needle biopsy (CNBx) and management remains controversial. Our objective was to define the incidence of malignancy in women diagnosed with pure LN on CNBx, and identify a subset of patients that may be observed. Patients diagnosed with LN on CNB between January 1993 and December 2010 were identified. Patients with an associated high-risk lesion or ipsilateral malignancy at time of diagnosis were excluded. All cases were reviewed by dedicated breast pathologists and breast imagers for pathologic classification and radiologic concordance, respectively. The study cohort was comprised of 184 (1.3 %) cases of pure LN (147 ALH, 37 LCIS) from 180 patients. Pathologic-radiologic concordance was achieved in 171 (93 %) cases. Excision was performed in 101 (55 %) cases and 83 (45 %) were observed. Mean follow-up was 50.3 (range, 6-212) months. Of cases excised, 1 of 81 (1.2 %) ALH and 1 of 20 (5 %) LCIS cases were upstaged to ductal carcinoma in situ (DCIS) and invasive lobular carcinoma (ILC), respectively. Only 1 of 101 (1 %) concordant lesions was upstaged on excision. Of the cases observed, 4 of 65 (6.2 %) developed ipsilateral cancer during follow-up: 1 of 51 (2 %) case of ALH and 3 of 14 (21.4 %) cases with LCIS (2 ILC, 2 DCIS). During follow-up, 2.9 % (4/138) patients with excised or observed LN developed a contralateral cancer. These data support that not all patients with LN diagnosed on CNB require surgical excision. Patients with pure ALH, demonstrating radiologic-pathologic concordance, may be safely observed.
    Annals of Surgical Oncology 07/2012; 19(10):3131-8. · 4.12 Impact Factor
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    ABSTRACT: The development of predictive biomarkers for IGF targeted anti-cancer therapeutics remains a critical unmet need. The insulin receptor A isoform (InsR-A) has been identified as a possible biomarker candidate but quantification of InsR-A in widely available formalin fixed paraffin embedded (FFPE) tissues is complicated by its similarities with the metabolic signaling insulin receptor isoform B (InsR-B). In the present study, qPCR based assays specific for InsR-A, InsR-B and IGF-1R were developed for use in FFPE tissues and tested for feasible use in clinical archived FFPE estrogen receptor (ER)+and ER- breast cancer tumors. FFPE compatible primer sets were designed with amplicon sizes of less than 60 base pairs and validated for target specificity, assay repeatability and amplification efficiency. FFPE tumors from ER+ (n=83) and ER-(n=64) primary untreated breast cancers, and ER+ hormone refractory (HR ER+) (n=61) breast cancers were identified for feasibility testing. The feasible use of InsR-A and InsR-B qPCRs were tested using all tumor groups and the feasibility of IGF-1R qPCR was determined using HR ER+ tumors. All qPCR assays were highly reproducible with amplification efficiencies between 96-104% over a 6 log range with limits of detection of 4 or 5 copies per reaction. Greater than 90% of samples were successfully amplified using InsR-A, InsR-B or IGF-1R qPCR primer sets and greater than 88% of samples tested amplified both InsR isoforms or both isoforms and IGF-1R. InsR-A was the predominant isoform in 82% ER+, 68% ER- and 100% HR ER+ breast cancer. Exploratory analyses demonstrated significantly more InsR-A expression in ER+ and HR ER+ groups compared to InsR-B (ER+ p<0.05, HR ER+ p<0.0005) and both groups had greater InsR-A expression when compared to ER- tumors (ER+ p<0.0005, HR ER+ p<0.05). IGF-1R expression of HR ER+ tumors was lower than InsR-A (p<0.0005) but higher than InsR-B (p<0.0005). The InsR-B expression of HR ER+ tumors was significantly reduced compared other tumor subgroups (ER+ and ER-, p<0.0005) and lead to a significant elevation of HR ER+ InsR-A: InsR-B ratios (ER+ and ER-, p<0.0005). The validated, highly sensitive InsR-A and InsR-B qPCR based assays presented here are the first to demonstrate the feasible amplification of InsR isoforms in FFPE tissues. Quantification data generated from this feasibility study indicating InsR-A is more predominant than InsR-B in breast cancer support the use of these assays for further investigation of InsR-A and InsR-B as predictive biomarkers for IGF targeted therapeutics.
    Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 04/2012; 22(3-4):108-15. · 2.35 Impact Factor
  • International journal of dermatology 01/2012; 51(1):72-4. · 1.18 Impact Factor
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    ABSTRACT: The role of estrogen receptor alpha (ERα) in breast cancer has been studied extensively, and its protein expression is prognostic and a primary determinant of endocrine sensitivity. However, much less is known about the role of ERβ and its relevance remains unclear due to the publication of conflicting reports. Here, we provide evidence that much of this controversy may be explained by variability in antibody sensitivity and specificity and describe the development, characterization, and potential applications of a novel monoclonal antibody targeting full-length human ERβ and its splice variant forms. Specifically, we demonstrate that a number of commercially available ERβ antibodies are insensitive for ERβ and exhibit significant cross-reaction with ERα. However, our newly developed MC10 ERβ antibody is shown to be highly specific and sensitive for detection of full-length ERβ and its variant forms. Strong and variable staining patterns for endogenous levels of ERβ protein were detected in normal human tissues and breast tumors using the MC10 antibody. Importantly, ERβ was shown to be expressed in a limited cohort of both ERα positive and ERα negative breast tumors. Taken together, these data demonstrate that the use of poorly validated ERβ antibodies is likely to explain much of the controversy in the field with regard to the biological relevance of ERβ in breast cancer. The use of the MC10 antibody, in combination with highly specific antibodies targeting only full-length ERβ, is likely to provide additional discriminatory features in breast cancers that may be useful in predicting response to therapy.
    Journal of Cellular Biochemistry 11/2011; 113(2):711-23. · 3.06 Impact Factor
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    ABSTRACT: Use of nipple-sparing mastectomy (NSM) is increasing. We sought to look at the role of NSM in BRCA mutation carriers. Tissue from women with a BRCA1 or BRCA2 mutation who underwent mastectomy between March 1987 and June 2009 at a single institution was reviewed. The entire nipple-areolar complex (NAC) was excised and histologically evaluated. The presence of terminal duct lobular units (TDLUs) and premalignant or malignant lesions in the NAC was noted. Sixty-two NACs from 33 women (25 BRCA1, 8 BRCA2) were studied. TDLUs were present in 15 (24%) NAC specimens. No evidence of atypical hyperplasia, carcinoma in situ, or invasive carcinoma was found in any of the 33 prophylactic mastectomy specimens. Among the 29 breasts with cancer and available tissue, 2 (7%) had malignant findings and 1 (3%) had atypia in the NAC. One woman who underwent bilateral mastectomy for bilateral invasive carcinoma had one nipple with tumor within lymphatics, and her contralateral nipple had atypical lobular hyperplasia. A second woman had ductal carcinoma in situ involving a single major lactiferous duct. The probability of nipple involvement by premalignant or malignant lesions in the NAC of BRCA mutation carriers is low at time of prophylactic mastectomy, but higher (10%) in women undergoing therapeutic mastectomy. NSM may be appropriate and oncologically safe for selected women with BRCA mutations. However, 24% of NACs contained TDLUs, with only 8% found in the nipple papilla; the significance of this for long-term risk is unknown.
    Annals of Surgical Oncology 10/2011; 18(11):3102-9. · 4.12 Impact Factor
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    ABSTRACT: Half of all breast cancers are early stage, lymph node negative, and hormone receptor positive. A 21-gene (Oncotype DX®; Genomic Health, Inc., Redwood City, CA) recurrence score (RS) is prognostic for recurrence and predictive of chemotherapy benefit. We explored the ability of oncologists to predict the RS using standard prognostic criteria. Standard demographic and tumor prognostic criteria were obtained from patients with an available RS. Two academic pathologists provided tumor grade, histologic type, and hormone receptor status. Six academic oncologists predicted the RS category (low, intermediate, or high) and provided a recommendation for therapy. The oncologists were then given the actual RS and provided recommendations for therapy. Analysis for agreement was performed. Thirty-one cases, including nine additional cases with variant pathology reads, were presented. There was substantial agreement in oncologists' ability to discriminate between true low or true intermediate and true high (κ = 0.75; p < .0001). Predictions between low and intermediate were not consistent. The most common discrepancies were predictions of a low RS risk when cases were true intermediate and predictions of an intermediate RS risk when cases were true low. The actual RS resulted in a change in the treatment recommendations in 19% of cases. Of the 186 scenarios and six oncologists in aggregate, five fewer chemotherapy recommendations resulted with the actual RS. Oncologists are able to differentiate between a low or intermediate RS and a high RS using standard prognostic criteria. However, provision of the actual RS changed the treatment recommendations in nearly 20% of cases, suggesting that the RS may reduce chemotherapy use. This effect was observed in particular in intermediate-risk cases. Prospective clinical trials are necessary to determine whether decisions based on the RS change outcomes.
    The Oncologist 09/2011; 16(10):1359-66. · 4.10 Impact Factor
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    ABSTRACT: p16, a nuclear protein encoded by the p16(INK4a) gene, is a regulator of cell-cycle regulation. Previous studies have shown that expression of p16 in tissue biopsies of patients with ductal carcinoma in situ (DCIS) is associated with increased risk of breast cancer, particularly when considered in combination with other markers such as Ki-67 and COX-2. Here, we evaluated how expression of p16 in breast tissue biopsies of women with atypical hyperplasia (AH), a putative precursor lesion to DCIS, is associated with subsequent development of cancer. p16 expression was assessed by immunohistochemistry in archival sections from 233 women with AH diagnosed at the Mayo Clinic. p16 expression in the atypical lesions was scored by percentage of positive cells and intensity of staining. We also studied coexpression of p16, with Ki-67 and COX-2, biomarkers of progression in AH. Risk factor and follow-up data were obtained via study questionnaire and medical records. Forty-seven patients (20%) developed breast cancer with a median follow-up of 14.5 years. Staining of p16 was increased in older patients relative to younger patients (P = 0.0025). Although risk of developing breast cancer was not associated with increased p16 expression, joint overexpression of Ki-67 and COX-2 was found to convey stronger risk of breast cancer in the first 10 years after diagnosis as compared with one negative marker (P < 0.01). However, the addition of p16 levels did not strengthen this association. p16 overexpression, either alone or in combination with COX-2 and Ki-67, does not significantly stratify breast cancer risk in women with AH.
    Cancer Prevention Research 09/2011; 4(12):1953-60. · 4.89 Impact Factor
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    ABSTRACT: Mammographic density is a strong risk factor for breast cancer but its underlying biology in healthy women is not well-defined. Using a novel collection of core biopsies from mammographically dense versus non-dense regions of the breasts of healthy women, we examined histologic and molecular differences between these two tissue types. Eligible participants were 40 + years, had a screening mammogram and no prior breast cancer or current endocrine therapy. Mammograms were used to identify dense and non-dense regions and ultrasound-guided core biopsies were performed to obtain tissue from these regions. Quantitative assessment of epithelium, stroma, and fat was performed on dense and non-dense cores. Molecular markers including Ki-67, estrogen receptor (ER) and progesterone receptor (PR) were also assessed for participants who had >0% epithelial area in both dense and non-dense tissue. Signed rank test was used to assess within woman differences in epithelium, stroma and fat between dense and non-dense tissue. Differences in molecular markers (Ki-67, ER, and PR) were analyzed using generalized linear models, adjusting for total epithelial area. Fifty-nine women, mean age 51 years (range: 40-82), were eligible for analyses. Dense tissue was comprised of greater mean areas of epithelium and stroma (1.1 and 9.2 mm(2) more, respectively) but less fat (6.0 mm(2) less) than non-dense tissue. There were no statistically significant differences in relative expression of Ki-67 (P = 0.82), ER (P = 0.09), or PR (P = 0.96) between dense and non-dense tissue. Consistent with prior reports, we found that mammographically dense areas of the breast differ histologically from non-dense areas, reflected in greater proportions of epithelium and stroma and lesser proportions of fat in the dense compared to non-dense breast tissue. Studies of both epithelial and stromal components are important in understanding the association between mammographic density and breast cancer risk.
    Breast Cancer Research and Treatment 08/2011; 131(1):267-75. · 4.47 Impact Factor
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    ABSTRACT: The authors describe the case of a 36-year-old man with gynecomastia who was previously treated with liposuction of the breast for cosmetic purposes. Histologic examination of a subsequent excisional biopsy revealed nests of displaced epithelial cells in adipose tissue. Epithelial cell displacement is a well-known risk of core needle biopsies and fine-needle aspirations of breast lesions. However, to the authors' knowledge, epithelial displacement in gynecomastia after liposuction, mimicking invasive ductal carcinoma, has not previously been reported.
    International Journal of Surgical Pathology 08/2011; 19(4):510-3. · 0.76 Impact Factor
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    ABSTRACT: Although occurrence of a second tumor is a well-recognized phenomenon in patients with a treated malignancy, simultaneous presentation with a second primary malignancy ("collision tumor") is rare in patients with breast cancer. We report a series of 7 patients who were undergoing axillary nodal staging of a newly diagnosed breast cancer. Six patients were found to have collision tumors in their axillary lymph nodes consisting of metastatic breast cancer and a previously unknown lymphoproliferative disorder. In 1 additional patient, a lymph node biopsy of a palpable axillary node resulted in the diagnosis of metastatic breast cancer and lymphoma. Awareness and diagnosis of such collision tumors will lead to appropriate management of each malignancy.
    Clinical Breast Cancer 03/2011; 11(1):61-6. · 2.42 Impact Factor
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    ABSTRACT: Mammographic breast density (MBD) is one of the strongest risk factors for breast cancer. Unfortunately, the biologic basis underlying this association is unknown. This study compared aromatase expression or immunoreactivity (IR) in core biopsies from mammographically dense versus non-dense regions of the breast to examine whether estrogen synthesis in the breast is associated with MBD and one possible mechanism through which MBD may influence breast cancer. Eligible participants were 40+ years, had a screening mammogram with visible MBD and no prior cancer or current endocrine therapy. Mammograms were used to identify dense and non-dense regions and ultrasound-guided core biopsies were performed to obtain tissue from these regions. Immunostaining for aromatase employed the streptavidin-biotin amplification method and #677 mouse monoclonal antibody. Aromatase IR was scored in terms of extent and intensity of staining for each cell type (stroma, epithelium, adipocytes) on histologic sections. A modified histological H-score provided quantitation of aromatase IR in each cell type and overall. Repeated measure analyses evaluated average differences (β(H)) in H-score in dense versus non-dense tissue within and across cell types. Forty-nine women with mean age 50 years (range: 40-82), participated. Aromatase IR was increased in dense (vs. non-dense) tissue in both the stroma (β(H) = 0.58) and epithelium (β(H) = 0.12) (P < 0.01). Adipocytes from non-dense tissue, however, had a greater IR compared to those from dense tissue (β(H) = -0.24, P < 0.01). An overall H-score which integrated results from all cell types demonstrated that aromatase IR was twice as great for dense (mean H-score = 0.90, SD = 0.53) versus non-dense (mean H-score = 0.45, SD = 0.39) breast tissue (β(H) = 0.45; P < 0.001). Overall, aromatase IR was greater for mammographically dense versus non-dense tissue and may partly explain how MBD influences breast cancer.
    Breast Cancer Research and Treatment 01/2011; 125(1):243-52. · 4.47 Impact Factor
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    ABSTRACT: The objective of this study was to describe the imaging findings of carcinoid tumors metastatic to the breast, with pathologic and clinical correlations. We searched our surgical database for cases of pathologically proven carcinoid tumors metastatic to the breast from October 1, 2000, to May 31, 2010. Of the approximate 10,000 breast biopsies identified, 7000 had malignant findings. Ten cases of metastatic carcinoid (0.1% of all malignancies), all with imaging studies available for review, were included in the study. All patients were women and had their primary carcinoid in the gastrointestinal tract (n=9) or lung (n = 1). One patient presented with a palpable breast mass and no history of carcinoid tumor; an ileal carcinoid was discovered after the pathologic diagnosis of metastatic carcinoid was established. In the breast, tumors presented as solitary lesions in half the cases. Metastases to the breast typically presented as circumscribed masses mammographically and as hypoechoic circumscribed masses ultrasonographically; some showed increased through-transmission and increased vascularity with color Doppler evaluation. Five patients had octreotide scans; of these, 4 had increased focal activity in the region of metastasis within the breast. Six patients underwent computed tomography. Without contrast, nodular masses were observed; with contrast, the masses showed rapid enhancement during arterial phase imaging. Magnetic resonance imaging (n = 4) also showed rapid enhancement and washout kinetics after contrast administration. Recognition of carcinoid metastases to the breast in patients with known or occult primary carcinoid tumors is important to avoid unnecessary treatment for primary breast cancer.
    Cancer Imaging 01/2011; 11:109-15. · 1.59 Impact Factor

Publication Stats

2k Citations
413.74 Total Impact Points


  • 2007–2013
    • Mayo Foundation for Medical Education and Research
      • Department of Surgery
      Rochester, MI, United States
  • 2002–2012
    • Mayo Clinic - Rochester
      • • Department of Surgery
      • • Department of Laboratory Medicine & Pathology
      • • Department of Radiology
      Rochester, Minnesota, United States
  • 2011
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 2008
    • University of Michigan
      Ann Arbor, Michigan, United States
  • 2005
    • Mayo Clinic - Scottsdale
      Scottsdale, Arizona, United States