Susann Schetter

Pediatric and adolescent breast masses: a review of pathophysiology, imaging, diagnosis, and treatment.

OBJECTIVE Pediatric breast masses are relatively rare and most are benign. Most are either secondary to normal developmental changes or neoplastic processes with a relatively benign behavior. To fully understand pediatric breast disease, it is important to have a firm comprehension of normal development and of the various tumors that can arise. Physical examination and targeted history (including family history) are key to appropriate patient management. When indicated, ultrasound is the imaging modality of choice. The purpose of this article is to review the benign breast conditions that arise as part of the spectrum of normal breast development, as well as the usually benign but neoplastic process that may develop within an otherwise normal breast. Rare primary carcinomas and metastatic lesions to the pediatric breast will also be addressed. The associated imaging findings will be reviewed, as well as treatment strategies for clinical management of the pediatric patient with signs or symptoms of breast disease. CONCLUSION The majority of breast abnormalities in the pediatric patient are benign, but malignancies do occur. Careful attention to patient presentation, history, and clinical findings will help guide appropriate imaging and therapeutic decisions.

Hematoma Formation During Breast Core Needle Biopsy in Women Taking Antithrombotic Therapy

OBJECTIVE The purpose of this study was to compare hematoma formation after breast core needle biopsy performed on patients undergoing and those not undergoing concurrent antithrombotic therapy. SUBJECTS AND METHODS A prospective assessment of core needle biopsies (stereotactic, ultrasound guided, or MRI guided) performed on patients enrolled between September 2011 and July 2012 formed the basis of this study. Postprocedure mediolateral and craniocaudal mammograms were evaluated for the presence and size of hematomas. Patients were clinically evaluated for complications 24-48 hours after the procedure through telephone call or face-to-face consultation. Needle size, type of biopsy, and presence of hematoma and documented complications were correlated with use of antithrombotic agents (including aspirin, warfarin, clopidogrel, and daily nonsteroidal antiinflammatory medications). RESULTS No clinically significant hematomas or bleeding complications were found. Eighty-nine of 617 (14.4%) non-clinically significant hematomas were detected on postprocedure mammograms. The probability of development of a non-clinically significant hematoma was 21.6% for patients taking antithrombotics and 13.0% for those not taking antithrombotics. Concurrent antithrombotic therapy and larger needle gauge were significant factors contributing to the probability of hematoma formation. The volume of the hematoma was not related to needle gauge or presence of antithrombotic therapy. CONCLUSION No clinically significant hematomas were found. Because there are potential life-threatening risks to stopping antithrombotic therapy before breast biopsy, withholding antithrombotic therapy for core needle breast biopsy is not recommended because the incidence of non-clinically significant hematoma is low.

Influence of Obesity on Breast Density Reduction by Omega-3 Fatty Acids: Evidence from a Randomized Clinical Trial.

Preclinical data indicate that omega-3 fatty acids (n-3FA) potentiate the chemopreventive effect of the antiestrogen (AE) tamoxifen against mammary carcinogenesis. The role of n-3FA in breast cancer prevention in humans is controversial. Preclinical and epidemiologic data suggest that n-3FA may be preferentially protective in obese subjects. To directly test the protective effect of n-3FA against breast cancer, we conducted a 2-year, open-label randomized clinical trial in 266 healthy postmenopausal women (50% normal weight, 30% overweight, 20% obese) with high breast density (BD; ≥25%) detected on their routine screening mammograms. Eligible women were randomized to one of the following five groups (i) no treatment, control; (ii) raloxifene 60 mg; (iii) raloxifene 30 mg; (iv) n-3FA lovaza 4 g; and (v) lovaza 4 g plus raloxifene 30 mg. The 2-year change in BD, a validated biomarker of breast cancer risk, was the primary endpoint of the study. In subset analysis, we tested the prespecified hypothesis that body mass index (BMI) influences the relationship between plasma n-3FA on BD. While none of the interventions affected BD in the intention-to-treat analysis, increase in plasma DHA was associated with a decrease in absolute breast density but only in participants with BMI >29. Our results suggest that obese women may preferentially experience breast cancer risk reduction from n-3FA administration. Cancer Prev Res; 9(4); 275–82. ©2015 AACR.

Stearoyl-CoA desaturase-1, a novel target of omega-3 fatty acids for reducing breast cancer risk in obese postmenopausal women

Background/Objectives:Conversion of saturated fatty acids to monounsaturated fatty acids by the enzyme stearoyl-Co-A-desaturase (SCD-1) is emerging as a major factor in promoting carcinogenesis including breast cancer. The aim of our study was to explore the regulation of SCD-1 by Raloxifene and omega-3 fatty acids in women at increased risk of breast cancer based on high breast density.Subjects/Methods:As a reflection of SCD-1 activity, we measured the ratios of palmitoleic acid (C16:1n7) to palmitic acid (C16:0) (SCD-16) and oleic acid (C18:1n9) to steric acid (C18:0) (SCD-18) in plasma samples of postmenopausal women enrolled in our clinical trial (NCT00723398) designed to test the effects of the antiestrogen, Raloxifene and/or the omega-3 preparation Lovaza, on breast density, a validated biomarker of breast cancer risk.Results:We report that Lovaza but not Raloxifene-reduced SCD-16 and SCD-18 for the 2-year duration of the trial. Importantly, decreasing levels of SCD-16 and SCD-18 were associated with a progressive reduction in breast density but only in obese women (body mass index ⩾30).Conclusions:Body mass index-related factors play an important role in the reduction of breast density and hence breast cancer risk by omega-3 fatty acids. SCD-1 may be a useful biomarker in future clinical trials testing the benefit of nutritional interventions in reducing obesity-associated breast cancer risk.

Frequencies of Private Mentions and Sharing of Mammography and Breast Cancer Terms on Facebook: A Pilot Study

Background The most popular social networking site in the United States is Facebook, an online forum where circles of friends create, share, and interact with each other’s content in a nonpublic way. Objective Our objectives were to understand (1) the most commonly used terms and phrases relating to breast cancer screening, (2) the most commonly shared website links that other women interacted with, and (3) the most commonly shared website links, by age groups. Methods We used a novel proprietary tool from Facebook to analyze all of the more than 1.7 million unique interactions (comments on stories, reshares, and emoji reactions) and stories associated with breast cancer screening keywords that were generated by more than 1.1 million unique female Facebook users over the 1 month between November 15 and December 15, 2016. We report frequency distributions of the most popular shared Web content by age group and keywords. Results On average, each of 59,000 unique stories during the month was reshared 1.5 times, commented on nearly 8 times, and reacted to more than 20 times by other users. Posted stories were most often authored by women aged 45-54 years. Users shared, reshared, commented on, and reacted to website links predominantly to e-commerce sites (12,200/1.7 million, 36% of all the most popular links), celebrity news (n=8800, 26%), and major advocacy organizations (n=4900, 15%; almost all accounted for by the American Cancer Society breast cancer site). Conclusions On Facebook, women shared and reacted to links to commercial and informative websites regarding breast cancer and screening. This information could inform patient outreach regarding breast cancer screening, indirectly through better understanding of key issues, and directly through understanding avenues for paid messaging to women authoring and reacting to content in this space.

Contralateral prophylactic mastectomy and patient mentions on Facebook

There is a gulf between patient utilization of contralateral prophylactic mastectomy (CPM) and national recommendations on CPM among women without elevated genetic or familial risk. In our view, this dissonance reflects a pressing need to educate our patients better. This in turn requires us to better understand and listen to our patients. The American Society of Breast Surgeons has recommended against CPM for women at average risk since mid‐2016, and the National Comprehensive Cancer Network has similarly discouraged CPM since late 2009. Despite this, CPM is an increasingly common choice for patients. Wong and colleagues recently found a more than tripling of the rate of CPM among women between 2002 and 2012, to nearly 13% of all women diagnosed in the SEER registry with unilateral Stages I to III breast cancer. Although a rational choice for CPM requires a significantly elevated risk of contralateral cancer, more than two‐thirds of CPM recipients did not have such risk elevation. Women at average risk have been found to choose CPM based on misperceptions of CPM benefits, future risk of contralateral breast cancer, cosmetic advantages, worry or anxiety, and preoperative contralateral MRI findings. Such perceptions on the part of our patients—despite the clear recommendations against CPM among peer societies—suggest that education has been insufficient to overcome what may be deep‐ seated subjective perceptions that are not aligned with objective evidence‐based data. To start to gauge the extent to which the general population discuss CPM and the extent to which objective mentions are made of benefits and risks, we recently piloted a brief national examination of all mentions of CPM on Facebook. Facebook is the industry‐leading online social network where opinions, sentiment and information are privately shared in a large circle of friends and acquaintances. In the context of CPM, such content could have positive or negative effects on the views of other women and their spouses, partners, relatives and friends. We contracted with Sysomos, an infomediary that resells Facebook data. We supplied Sysomos with these keywords: Double mastectomy, Contralateral mastectomy, Prophylactic mastectomy, Risk‐ reducing mastectomy, Risk‐reduction mastectomy, Bilateral mastectomy, Preventive mastectomy, Voluntary mastectomy, Preventative mastectomy, and Removal of both breasts. Sysomos made a software‐as‐a‐ service dashboard available to us (Figure 1) to track results and gave us aggregate data on the number of Facebook users mentioning these terms over a 30‐day period, reactions to these, and the frequency of mentions of other words in the context of postings on CPM. This publicly available, deidentified aggregate data did not require IRB approval in our institution. Facebook categorizes content as a story (a posted item of content by a user), or any type of interaction which can be a reshare (a reposting of an original story to another user connected to the sharing user), a comment (a text comment made by a connected user on the original story or on a prior comment), or a reaction (one of a number of emoji representing emotions including positive, negative, empathetic, surprise, love, etc). Over the 30 day period between April 25, 2017 and May 25, 2017, there were a total of 155 000 Facebook users in the United States who posted, shared, re‐shared, or interacted (ie, emoji, comments) with a total of 163 200 content items meeting the inclusion criteria. Most users were female (83%), and representation by age category was low among the young: 18‐24 year old (4%) and 25‐34 (15%) compared to the 35‐ to 44‐year group (24%), the 45‐54 (26%), 55‐64 (18%), and 65+ (13%). CPM‐related stories were relatively infrequent, with only 2900 authors posting 3200 unique stories over the month. However, each story was on average shared approximately 1 time, commented on 16 times, and reacted to 32 times over the month. Over the month, there were substantial regular dips in usage, coinciding with weekends (Figure 1). Facebook also makes available “trending” content, in particular of the ten most popular website links that were posted, shared, Received: 25 July 2017 | Revised: 26 July 2017 | Accepted: 28 February 2018 DOI: 10.1111/tbj.13079

Diagnosis and imaging characteristics of a juvenile fibroadenoma in a 2–year-old patient: a case report

Fibroadenomas are abundantly reported in the literature with several papers documenting the natural progression and clinical outcomes of thousands of cases. Juvenile fibroadenomas (also called cellular fibroadenomas) are frequently characterized by rapid growth, often described as 5-10 cm in size. They constitute approximately 7%-8% of fibroadenomas. They often measure greater than 5 cm. Pathologically, they show similar features to fibroadenomas but can resemble phyllodes. There have been few documented cases of breast masses in early childhood. Furthermore, there are scant radiology publications focused on the imaging features of juvenile fibroadenomas in patients younger than 5 years old. Our patient presented at 2 years of age with a unilateral right breast mass. Two ultrasound examinations were completed over a period of 5 months, and a magnetic resonance imaging was performed prior to surgical intervention. Eventual surgical excision yielded a final pathologic diagnosis of juvenile fibroadenoma. In this report, we will discuss the imaging and pathology of juvenile fibroadenomas, and we will address important differential considerations both from a pathologic and radiologic standpoint.

Abstract 236: Stearoyl-CoA desaturase-1, a novel target of omega-3 fatty acids for reducing breast cancer risk in obese postmenopausal women

Preclinical and epidemiologic data suggest that a unique feature of lipogenesis in cancer cells which has received limited attention is the accumulation of monounsaturated fatty acids (MUFA) which are largely derived from saturated fatty acids (SFA) by the action of stearoyl-Co-A desaturase (SCD-1). Activation of SCD-1, a delta-9 fatty acid desaturase, is considered to be an important factor in the development of obesity and several types of cancer including breast cancer. However, no data are available on how changes in SCD-1 activity induced by potential chemopreventive agents relate to established biomarkers of breast cancer risk. To address this issue, we measured the activity of SCD-1, expressed as the ratios of palmitoleic acid (C16:ln7) to palmitic acid (C16:0) (SCD-16) and oleic acid (C18:ln9) to steric acid (C18:0) (SCD-18) in plasma samples of postmenopausal women enrolled in our recently published clinical trial (Sandhu N, et al Cancer Prev Res 9:275, 2016) designed to test the individual and combined effect of the antiestrogen Raloxifene and the omega-3 preparation Lovaza on breast density, a validated biomarker of breast cancer risk. We observed that daily administration of Lovaza (1,860 mg eicosapentaenoic [EPA] + 1,500 mg docosahexaenoic [DHA]) significantly reduced SCD-1 activity, an effect which was sustained for the two-year duration of the trial. Raloxifene, on the other hand, did not significantly alter SCD-1 activity in our subjects. SCD-1 activity was positively correlated with BMI (for SCD-16, r=0.45, p Citation Format: Andrea Manni, John P. Richie, Susann E. Schetter, Ana Calcagnotto, Neil Trushin, Cesar Aliaga, Karam El-Bayoumy. Stearoyl-CoA desaturase-1, a novel target of omega-3 fatty acids for reducing breast cancer risk in obese postmenopausal women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 236. doi:10.1158/1538-7445.AM2017-236

Abstract 1904: Randomized clinical trial testing the efficacy of the combination of omega-3-fatty acids (n-3FA) and the antiestrogen raloxifene in reducing breast density (BD) in postmenopausal women

Our preclinical data indicate that n-3FA potentiate the chemopreventive effects of the antiestrogen (AE) Tamoxifen against mammary tumorigenesis induced by 1-methyl-1-nitrosourea in female Sprague Dawley rats.(A. Manni et al. Int. J. of Cancer 2014; 134:1549).To test the clinical impact of this approach we conducted a randomized clinical trial in healthy postmenopausal women at increased risk of breast cancer based on BD ≥ 25% detected at their routine annual screening mammogram. Out of 784 eligible subjects, 266 women were randomly assigned to one of the following groups 1) Control 2) The AE Raloxifene 60mg 3) Raloxifene 30mg 4) Lovaza 4g (the FDA approved n-3FA formulation containing EPA + DHA), 5) Lovaza 4gm plus Raloxifene 30mg. The rationale for choosing a dose of Raloxifene half the conventional dose of 60mg to be tested in combination was in the attempt to reduce toxicity while preserving antitumor action as supported by our preclinical studies with Tamoxifen (A. Manni et al. Canc. Prev. Res 2010; 3:322). The groups were comparable with regard to baseline demographics including age, BMI, parity, age at first child birth, family history of breast cancer, and history of prior breast biopsies. The duration of the intervention was 2 years and the change in breast density at year one and two was the primary endpoint. Breast density, a well established biomarker of breast cancer risk, was measured by the volumetric method using the Volpara software. Two hundred and fourteen women (∼80%) completed the trial. Compliance was excellent as assessed by pill counts (>95%) and plasma fatty acid analysis using gas chromatography-flame ionization (GC-FID) detection which showed the expected rise in n-3FA levels in the groups receiving Lovaza. Toxicity was minimal with vasomotor symptoms being more frequent in the groups receiving Raloxifene (13.2% with 30mg and 22.6% with 60mg) and gastrointestinal events more frequent in the combination group. No subject experienced thromboembolic events. The combination group exhibited the most beneficial changes in lipid panel with reduction in LDL (low density lipoprotein) cholesterol, triglyceride and increase in HDL (high density lipoprotein) cholesterol. Compared to control, none of the interventions significantly affected percent or absolute breast density at either year one or two. Our results indicate that in this group of healthy postmenopausal women the combination of Lovaza and Raloxifene at less than the conventional dose (e.g. 30mg), while feasible and well tolerated did not reduce breast cancer risk as assessed by a decrease in breast density. (This work has been funded by Susan G. Komen for the Cure, KG081632). Citation Format: Narinder Sandhu, Susann E. Schetter, Jason Liao, Terryl J. Hartman, John P. Richie, Karam El-Bayoumy, Bogdan Prokopczyk, Cindy DuBrock, Carina Signori, Christopher Hamilton, Laurence M. Demers, Andrea Manni. Randomized clinical trial testing the efficacy of the combination of omega-3-fatty acids (n-3FA) and the antiestrogen raloxifene in reducing breast density (BD) in postmenopausal women. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1904. doi:10.1158/1538-7445.AM2015-1904

Abstract 3249: Differential impact of body mass index (BMI) on absolute and percent breast density; implications regarding their use as breast cancer risk (BCR) biomarkers

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Percent breast density (PBD) is a commonly used biomarker of BCR. However, its use is greatly confounded by the strong influence of non-dense breast tissue on its measurement and factors, such as BMI, which have a direct impact on this non-dense tissue. Consequently, BMI, a potent BCR factor, is actually negatively correlated with PBD. We propose that absolute breast density (ABD), a more direct determinant of BCR which can be easily and accurately measured on a routine basis, is a more accurate and valid biomarker of BCR. To address this issue, we compared the correlation between PBD and ABD with baseline demographics (e.g., age, BMI, waist:hip ratio, reproductive parameters, family history of BC and personal history of breast biopsies) and dietary and physical activity variables (measured using a modified version of the NCI Diet History Questionnaire and the International Physical Activity Questionnaire, respectively) in a group of 169 healthy postmenopausal women enrolled in a chemoprevention trial testing the individual and combined effects of the antiestrogen Raloxifene and the omega-3 preparation Lovaza on BD used as a biomarker of BCR ([NCT00723398][1]). A volumetric breast density software (Volpara, Matakina, Wellington, New Zealand) was used for determination of ABD and PBD since it may be superior to the two-dimensional method in predicting BCR. As observed previously, a strong negative correlation between PBD and BMI was observed (Rho = -0.5, P<5e-12) due to the strong positive correlation of BMI with non-dense breast. However, we also observed a strong positive correlation of BMI with ABD (Rho = 0.41, P<2.5e-8), a relationship which is not well established in the literature and supports the use of ABD as a more accurate indicator of BCR. We also observed that correction of PBD by BMI did not frequently provide the same information as ABD, thus further indicating that the latter should be the gold standard for BD measurement. The strong positive association between BMI and ABD implies that even a modest change in BMI (as can be expected with dietary and physical activity manipulations) is likely to obscure the independent effect of an intervention on ABD. We indeed observed that many correlations between dietary variables and ABD did not emerge until adjustment was made for BMI. Our data support the following conclusions: 1) ABD instead of PBD (even after adjustment for BMI) should be used for assessment of BD; 2) based on our novel observation of the strong positive correlation between BMI and ABD, ABD should be adjusted for BMI when testing the influence of an intervention on BD as a biomarker of BCR. (Supported by grant KG081632 from Susan G. Komen for the Cure.) Citation Format: Susann Schetter, Terryl Hartman, Jason Liao, John P. Richie, Bogdan Prokopczyk, Cynthia Dubrock, Carina Signori, Christopher Hamilton, Laurence M. Demers, Karam El-Bayoumy, Andrea Manni. Differential impact of body mass index (BMI) on absolute and percent breast density; implications regarding their use as breast cancer risk (BCR) biomarkers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3249. doi:10.1158/1538-7445.AM2014-3249 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00723398&atom=%2Fcanres%2F74%2F19_Supplement%2F3249.atom