Daniel Visscher

Clinicopathologic analysis of solid papillary carcinoma of the breast and associated invasive carcinomas.

Solid papillary carcinomas (SPCs) are uncommon tumors composed of circumscribed large cellular nodules separated by bands of dense fibrosis. The aim of this study was to further elucidate the characteristics of SPC, the types and significance of invasive carcinomas associated with these tumors, and the long-term clinical outcome. Fifty-eight SPCs were analyzed (mean follow-up, 9.4 years). Cases were divided into three groups: 1) SPC only (32.7%), 2) SPC with extravasated mucin (8.6%), and 3) SPC with invasive components (58.7%) consisting of neuroendocrine-like (29.5%), colloid (23.5%), ductal not otherwise specified (14.5%), lobular (3%), tubular (3%), or mixed (26.5%). The mean age was 72 years. All were estrogen receptor positive and 86% were histologic grade 1. The total size of the tumor measured 0.3 to 15 cm. In the group with invasive carcinoma, the size of invasion was 0.1 to 4 cm. Axillary nodes were involved in 13% of the cases (6 of 46); all of these had an invasive component in the primary tumor. Local recurrence was seen in 5 patients, all from the group with invasive carcinoma. Overall, 11.7% died of their tumor, 1 to 4 years after diagnosis (mean, 2.3 years); none of them belongs to the group of noninvasive SPC. Five of the 6 patients who died of tumor had invasive components. The sixth patient who died with “metastatic signet-ring cell carcinoma” at 10 years was in the group of patients with SPC with extravasated mucin where the SPC lesion had prominent signet-ring cell features. In conclusion, SPCs are heterogeneous lesions that arise in older women and have an indolent behavior. Lymph node and distant metastases are uncommon and generally limited to cases with (conventional) invasive components.

Ductal carcinoma in situ in African American versus Caucasian American women: analysis of clinicopathologic features and outcome.

Invasive breast carcinoma has a more aggressive phenotype and a higher mortality rate in African American (AA) than in Caucasian American (CA) women. The characteristics of ductal carcinoma in situ (DCIS) in the AA population have not been extensively studied.

Atypical apocrine adenosis of the breast: long-term follow-up in 37 patients.

CONTEXT Atypical apocrine adenosis is a rare breast lesion in which the cellular population demonstrates cytologic alterations that may be confused with malignancy. The clinical significance and management of atypical apocrine adenosis are unclear because of the lack of long-term follow-up studies. OBJECTIVE To determine the breast cancer risk in a retrospective series of patients with atypical apocrine adenosis diagnosed in otherwise benign, breast excisional biopsies. DESIGN We identified 37 atypical apocrine adenosis cases in the Mayo Benign Breast Disease Cohort (9340 women) between 1967 and 1991 with a blinded pathology rereview. Breast cancer diagnoses subsequent to initial atypical apocrine adenosis biopsy were identified (average follow-up, 14 years). RESULTS The mean age at diagnosis of atypical apocrine adenosis in the group was 59 years. Breast carcinoma subsequently developed in 3 women (8%) with atypical apocrine adenosis, diagnosed after follow-up intervals of 4, 12, and 18 years. The tumor from 1 of the 3 cases (33%) was ductal carcinoma in situ, contralateral to the original biopsy, and the other 2 cases (66%) were invasive carcinoma. Ages at the time of diagnosis of atypical apocrine adenosis were 55, 47, and 63 years for those that developed in situ or invasive carcinoma. CONCLUSIONS (1) Atypical apocrine adenosis was a rare lesion during the accrual era of our cohort (<1% of cases); (2) women found to have atypical apocrine adenosis were, on average, older than were other patients with benign breast disease, however, there does not seem to be an association with age and risk for developing carcinoma in patients diagnosed with atypical apocrine adenosis, as previously suggested; and (3) atypical apocrine adenosis does not appear to be an aggressive lesion and should not be regarded as a direct histologic precursor to breast carcinoma.

Regional Differences in Breast Cancer Biomarkers in American Indian and Alaska Native Women

Background: Breast cancer is not a homogeneous disease, but several different and unique subtypes defined by gene expression analysis. Incidence and mortality rates vary by almost 3-fold between Alaska (highest) and the Southwestern tribes (lowest). We hypothesized that these differences may be due to, in part, varying levels of biologic tumor aggressiveness. Methods: A biorepository of the North Central Cancer Treatment Group with 95 cases of American Indian and Alaska Native (AIAN) women with adenocarcinoma of the breast surgically treated from 1990 to 2000 was tested for several biomarkers. Comparison distributions of biomarker values across state of residence using t tests for continuous (p53, MIB-1, cyclin D) and ordinally scaled markers [EGF receptor (EGFR), BCL-2, Her2] and χ2 tests of significance for binary markers [estrogen receptor (ER), progesterone receptor (PR)] were done. Results: Significant regional differences in some biomarker expression levels were seen. No increase was observed in “triple-negative” breast cancer or Her2 overexpression in these cases. Conclusions: Despite a 3-fold difference in breast cancer mortality in Alaska Native versus Southwestern American Indians, standard biomarkers such as ER, PR, and Her2 neu expression did not explain the disparity. Impact: There is a need for research to understand the biologic basis of breast cancer disparities in AIAN women. Potential for a prospective trial will be explored with tribes. See all articles in this CEBP Focus section, “Community Network Program Centers.” Cancer Epidemiol Biomarkers Prev; 23(3); 409–15. ©2014 AACR.

Minimal Free Resolutions of Complete Bipartite Graph Ideals

This paper gives an explicit construction for the minimal free resolution of a complete bipartite graph ideal. This yields a combinatorial formula for the Betti numbers and projective dimension of complete bipartite graph ideals.

Equilibrium measures for certain isometric extensions of Anosov systems

We prove that for the frame flow on a negatively curved, closed manifold of odd dimension other than 7, and a Holder continuous potential that is constant on fibers, there is a unique equilibrium measure. We prove a similar result for automorphisms of the Heisenberg manifold fibering over the torus. Our methods also give an alternate proof of Brin and Gromovs result on the ergodicity of these frame flows.

A Case Study of Student and Instructor Reactions to a Calculus E-Book

Abstract This article details the results of testing an e-book in two differential calculus classes. Although we, as math instructors, were drawn to the components of the e-book that promote conceptual understanding—such as the interactive figures—the students reported liking the assessment support most. We found that students were initially excited about the interactive figures, but the majority did not use them much over the term. The students who did make use of the interactive figures, however, also reported that the figures improved their understanding of calculus concepts.

A Franks' lemma for convex planar billiards

Let γ be an orbit of the billiard flow on a convex planar billiard table; then the perpendicular part of the derivative of the billiard flow along γ is a symplectic linear map DP. This paper contains a proof of the following Franks’ lemma for a residual set of convex planar billiard tables: for any closed orbit, the map DP can be perturbed freely within a neighbourhood in Sp(1) by a C2-small perturbation in the space of convex planar billiard tables.

Abstract B39: Mammographic density and breast lobular involution

B39 Background The breast glandular epithelium is composed of lobules that undergo age-related involution that increases as women age and has been associated with lowered breast cancer risk. Mammographic density (MD) is an established risk factor for breast cancer that has been shown to decrease with age. This study examined the association of age-related lobular involution with mammographic breast density. Materials and Methods The study sample was selected from approximately 20,000 healthy women who were enrolled in a screening cohort at the Mayo Clinic (Mayo Mammography Health Study) from 2003 to 2006 and had a benign breast biopsy (BBD) within 2 years of the enrollment mammogram. A quantitative measure of mammographic density, percent density (PD) was estimated on the enrollment mammogram, in addition to its components dense and nondense area (NDA). All biopsies were reviewed by a breast pathologist for the type of benign breast disease (BBD) as well as lobular involution status. Involution was defined as the proportion of terminal ductal lobular units (TDLUs) in the background tissue on biopsy that showed at least 50% decrease in size and number of acini from normal lobules and was subjectively assessed as: No- 0% involution, Partial- 1 to 74%, or Complete- >75% involution. Mean density was estimated for the 3 categories of involution using generalized linear models and square root transformation. Confounders were assessed including age, parity, body mass index (BMI), type of BBD, menopausal status, age at first birth and family history Results A total of 317 women from the MMHS had BBD within 2 years of enrollment. Mean age at BBD diagnosis in this sample was 55 years. Age- and BMI- adjusted analyses suggested an inverse association of involution and percent density with adjusted mean PD values of 23.3 (95%CI [17.2, 30.3]) for no involution, 21.9 (95%CI [20.0, 23.9]) for partial involution, and 17.8 (95% CI [14.7, 21.3]) for complete involution (p for trend 0.05). This trend was driven primarily by the positive association of involution with nondense area with adjusted mean NDA values of 103.1cm2 (95% CI [86.1, 121.7]) for no involution, 104.9 cm2 (95% CI [99.4, 110.7]) for partial involution, and 126.2 cm2 (95% CI [115.0, 137.9]) for complete involution (p for trend 0.004). Discussion Our findings suggest that MD is inversely associated with involution of breast tissues, providing a plausible mechanism through which MD influences breast cancer risk. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B39.