Browsing by Subject "Breast"

Now showing 1 - 10 of 18
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    Adenomyoepithelioma of the Breast in the Setting of Prior Contralateral Breast Malignancy
    (Springer Nature, 2023-05-18) Dauterman, Leah C.; Lentsch, Kristen; Fan, Betty; Medicine, School of Medicine
    An 81-year-old female patient underwent a screening mammogram one year after completing treatment for right-sided estrogen receptor (ER)/progesterone receptor (PR)-negative ductal carcinoma in situ (DCIS). A new 1-cm mass was noted in the contralateral breast. Ultrasound and percutaneous core needle biopsy results were suggestive of an atypical papillary lesion. An excisional biopsy was performed, and the final pathology was consistent with a benign adenomyoepithelioma (AME). Surgical resection was considered her definitive treatment. AME of the breast is a rare clinical entity, with only a handful of case reports and case series available. In this case report, we review common clinical and radiologic presentations, methods of diagnosis, and recommendations for management based on current literature. The presence of an AME in the background of a previous or synchronous breast malignancy occurs in a very small percentage of cases. On review of available literature, we identified other cases with a past or current history of breast malignancy.
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    Breast calcifications following electrical defibrillation: An unusual mammographic appearance
    (Radiology Case Reports U of Washington, 2010) Westphal, Steven M.; Jani, Manish; Badve, Sunil; Department of Radiology and Imaging Sciences, IU School of Medicine
    We present a case of a 57-year-old woman with a past medical history of end-stage renal disease and a recent history of electrical defibrillation who arrived for her annual mammogram with no breast-related complaints. The mammogram showed interval development of unusual clusters of heterogeneous calcifications. The patient underwent stereotactic core-needle biopsy for definitive diagnosis. The pathologic evaluation revealed fibrosis, abnormal adipocytes, and calcifications with no evidence of malignancy. The constellation of findings was consistent with fat necrosis and fibrosis related to tissue damage sustained during the recent defibrillation.
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    Dual PI3K and Wnt pathway inhibition is a synergistic combination against triple negative breast cancer
    (Springer Nature, 2017-04-26) Solzak, Jeffrey P.; Atale, Rutuja V.; Hancock, Bradley A.; Sinn, Anthony L.; Pollok, Karen E.; Jones, David R.; Radovich, Milan; Surgery, School of Medicine
    Triple negative breast cancer accounts for 15-20% of all breast cancer cases, but despite its lower incidence, contributes to a disproportionately higher rate of mortality. As there are currently no Food and Drug Administration-approved targeted agents for triple negative breast cancer, we embarked on a genomic-guided effort to identify novel targeted modalities. Analyses by our group and The Cancer Genome Atlas have identified activation of the PI3K-pathway in the majority of triple negative breast cancers. As single agent therapy is commonly subject to resistance, we investigated the use of combination therapy against compensatory pathways. Herein, we demonstrate that pan-PI3K inhibition in triple negative breast cancers results in marked activation of the Wnt-pathway. Using the combination of two inhibitors currently in clinical trial as single agents, buparlisib(pan-PI3K) and WNT974(WNT-pathway), we demonstrate significant in vitro and in vivo synergy against triple negative breast cancer cell lines and xenografts. Taken together, these observations provide a strong rationale for testing dual targeting of the PI3K and WNT-pathways in clinical trials.
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    Estimating breast tissue-specific DNA methylation age using next-generation sequencing data
    (Springer, 2020-03-12) Castle, James R.; Lin, Nan; Liu, Jinpeng; Storniolo, Anna Maria V.; Shendre, Aditi; Hou, Lifang; Horvath, Steve; Liu, Yunlong; Wang, Chi; He, Chunyan; Medical and Molecular Genetics, School of Medicine
    Background DNA methylation (DNAm) age has been widely accepted as an epigenetic biomarker for biological aging. Emerging evidence suggests that DNAm age can be tissue-specific and female breast tissue ages faster than other parts of the body. The Horvath clock, which estimates DNAm age across multiple tissues, has been shown to be poorly calibrated in breast issue. We aim to develop a model to estimate breast tissue-specific DNAm age. Methods Genome-wide DNA methylation sequencing data were generated for 459 normal, 107 tumor, and 45 paired adjacent-normal breast tissue samples. We determined a novel set of 286 breast tissue-specific clock CpGs using penalized linear regression and developed a model to estimate breast tissue-specific DNAm age. The model was applied to estimate breast tissue-specific DNAm age in different breast tissue types and in tumors with distinct clinical characteristics to investigate cancer-related aging effects. Results Our estimated breast tissue-specific DNAm age was highly correlated with chronological age (r = 0.88; p = 2.9 × 10−31) in normal breast tissue. Breast tumor tissue samples exhibited a positive epigenetic age acceleration, where DNAm age was on average 7 years older than respective chronological age (p = 1.8 × 10−8). In age-matched analyses, tumor breast tissue appeared 12 and 13 years older in DNAm age than adjacent-normal and normal breast tissue (p = 4.0 × 10−6 and 1.0 × 10−6, respectively). Both HER2+ and hormone-receptor positive subtypes demonstrated significant acceleration in DNAm ages (p = 0.04 and 3.8 × 10−6, respectively), while no apparent DNAm age acceleration was observed for triple-negative breast tumors. We observed a non-linear pattern of epigenetic age acceleration with breast tumor grade. In addition, early-staged tumors showed a positive epigenetic age acceleration (p = 0.003) while late-staged tumors exhibited a non-significant negative epigenetic age acceleration (p = 0.10). Conclusions The intended applications for this model are wide-spread and have been shown to provide biologically meaningful results for cancer-related aging effects in breast tumor tissue. Future studies are warranted to explore whether breast tissue-specific epigenetic age acceleration is predictive of breast cancer development, treatment response, and survival as well as the clinical utility of whether this model can be extended to blood samples.
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    Ethnicity-dependent and -independent heterogeneity in healthy normal breast hierarchy impacts tumor characterization
    (Nature Publishing Group, 2015-08-27) Nakshatri, Harikrishna; Anjanappa, Manjushree; Bhat-Nakshatri, Poornima; Department of Surgery, IU School of Medicine
    Recent reports of widespread genetic variation affecting regulation of gene expression raise the possibility of significant inter-individual differences in stem-progenitor-mature cell hierarchy in adult organs. This has not been explored because of paucity of methods to quantitatively assess subpopulation of normal epithelial cells on individual basis. We report the remarkable inter-individual differences in differentiation capabilities as documented by phenotypic heterogeneity in stem-progenitor-mature cell hierarchy of the normal breast. Ethnicity and genetic predisposition are partly responsible for this heterogeneity, evidenced by the finding that CD44+/CD24- and PROCR+/EpCAM- multi-potent stem cells were elevated significantly in African American women compared with Caucasians. ALDEFLUOR+ luminal stem/progenitor cells were lower in BRCA1-mutation carriers compared with cells from healthy donors (p = 0.0014). Moreover, tumor and adjoining-normal breast cells of the same patients showed distinct CD49f+/EpCAM+ progenitor, CD271+/EpCAM- basal, and ALDEFLUOR+ cell profiles. These inter-individual differences in the rate of differentiation in the normal breast may contribute to a substantial proportion of transcriptome, epigenome, and signaling pathway alterations and consequently has the potential to spuriously magnify the extent of documented tumor-specific gene expression. Therefore, comparative analysis of phenotypically defined subpopulations of normal and tumor cells on an individual basis may be required to identify cancer-specific aberrations.
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    Immediate Bilateral Breast Reconstruction with Unilateral Deep Superior Epigastric Artery and Superficial Circumflex Iliac Artery Flaps
    (KoreaMed Synapse, 2016-09) Hansen, Keith S.; Gutwein, Luke G.; Hartman, Brett C.; Sood, Rajiv; Socas, Juan; Department of Surgery, IU School of Medicine
    Autologous breast reconstruction utilizing a perforator flap is an increasingly popular method for reducing donor site morbidity and implant-related complications. However, aberrant anatomy not readily visible on computed tomography angiography is a rare albeit real risk when undergoing perforator flap reconstruction. We present an operative case of a patient who successfully underwent a bilateral breast reconstruction sourced from a unilateral abdominal flap divided into deep superior epigastric artery and superficial circumflex iliac artery flap segments.
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    Increased epigenetic age in normal breast tissue from luminal breast cancer patients
    (Biomed Central, 2018-08-29) Hofstatter, Erin W.; Horvath, Steve; Dalela, Disha; Gupta, Piyush; Chagpar, Anees B.; Wali, Vikram B.; Bossuyt, Veerle; Storniolo, Anna Maria; Hatzis, Christos; Patwardhan, Gauri; Von Wahlde, Marie-Kristin; Butler, Meghan; Epstein, Lianne; Stavris, Karen; Sturrock, Tracy; Au, Alexander; Kwei, Stephanie; Pusztai, Lajos; Medicine, School of Medicine
    BACKGROUND: Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue. RESULTS: Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank (n = 25) and from non-cancer-related breast surgery specimens (n = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the "Epigenetic Clock," a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age (r = 0.712, p < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue (p = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue (p = 0.012). CONCLUSIONS: Women with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk.
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    Lymphoepithelial Carcinoma of the Breast Treated With Partial Mastectomy and Sentinel Lymph Node Biopsy
    (Springer Nature, 2023-05-18) Lentsch, Kristen; Dauterman, Leah C.; Fan, Betty; Surgery, School of Medicine
    Lymphoepithelial carcinoma of the breast (LELC) is a rarely encountered form of breast carcinoma, and there is limited information treatment for this entity. We present a case of a 55-year-old postmenopausal female presenting with a left breast mass on screening mammogram with core needle biopsy showing lymphoepithelial carcinoma. The patient was treated with surgical resection of the mass and sentinel lymph node biopsy, followed by adjuvant chemotherapy and radiation. Given the rarity of this type of breast carcinoma, our case study continues to add to the treatment considerations in the literature, specifically the role of sentinel lymph node.