bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triple-negative invasive breast cancer (TNBC): Mammographic, US, and MR imaging features according to androgen receptor (AR) expression.
Authors: Moon Woo Kyung 
Published: February 2017

159 Background: A subset of TNBC is characterized by an androgen gene signature and early clinical trials have demonstrated clinical benefit with the use of the AR antagonist, bicalutamide, for the treatment of patients with AR+, estrogen receptor/progesterone receptor- breast cancer. Methods: AR expression was assessed immunohistochemically in 125 patients (median age; 54 years, range; 26-82 years) with TNBC from a consecutive series of 1,086 operable invasive breast cancers. Two experienced breast imaging radiologists (6 and 24 years of experience, respectively) reviewed the mammograms, US, and MR images without knowledge of clinicopathologic findings. The imaging and pathologic features of 33 AR-positive TNBCs were compared with those of 92 AR-negative TNBCs by using the Fisher’s exact or chi-squared tests. Results: AR expression in TNBC is significantly associated with mammographic findings (P < 0.001), lesion type at MR imaging (P < 0.001), and mass shape or margin at ultrasound (P < 0.001; P= 0.002). The highest PPVs for AR-positive cancer were non-mass enhancement on MR imaging (PPV, 1.00; 95% CI: 0.61, 1.00), calcifications only seen on mammography (PPV, 1.00; 95% CI: 0.37, 1.00), and spiculated masses on US (PPV, 1.00; 95% CI: 0.22, 1.00). Conclusions: AR-positive and AR-negative tumors have distinct imaging features in TNBC. The presence of calcifications or focal asymmetries at mammography, the presence of echogenic halo or non-complex hypoechoic masses at US, masses with irregular shape or indistinct margins at mammography and US, and masses with irregular shape or spiculated margins, or non-mass lesions at MR imaging were associated with AR expression in TNBC. These imaging features may be used to predict AR status, which could assist in treatment planning, prediction of response, and assessment of prognosis for patients with TNBC.
Prevalence of BRCA2 mutations and other clinical characteristics in women with triple-negative breast cancer.
Authors: Chun Jennifer , Schnabel Freya Ruth , Schwartz Shira , Billig Jessica , Hiotis Karen , Guth Amber , Axelrod Deborah M. 
Published: February 2017

160 Background: Triple-negative breast cancers (TNBC) represent 10%–20% of invasive breast cancers. Current guidelines recommend genetic testing for women who are diagnosed with TNBC. Studies have shown that BRCA1 mutations are associated with TNBC, but there is little information on the relationship of BRCA2 mutations and TNBC. The purpose of this study was to look at the clinical characteristics of TNBC compared to non-TNBC in a cohort of women with newly diagnosed breast cancer. Methods: The Breast Cancer Database at our institution was queried for patients with invasive breast cancer. We included the following variables: age, race, BRCA1,2, tumor characteristics, and personal history of breast cancer (PHBC). Statistical analyses included Pearson’s Chi-Square and Fisher’s Exact Tests. Results: Out of a total of 1,332 women, 125 (9%) had TNBC. The median age for both TNBC and non-TNBC was 59 years. Majority of women had early stage breast cancer (92%) with ductal carcinoma (80%). There was a significantly higher proportion of Blacks and Asians with TNBC (p < 0.0001). Women with TNBC had higher Ki-67 (p < 0.0001). Within the TNBC group, there were 12 (29%) patients who tested positive for BRCA1,2 mutation and 23 (8%) who tested positive for BRCA 1,2 mutations in the non-TNBC group. Interestingly, BRCA1 was not associated with TNBC (p = 0.40) and BRCA2 was significantly associated with TNBC (p < 0.0001). We also found a higher proportion of TNBC in women who had a PHBC (p = 0.01). Conclusions: In our study, women with TNBC were similar in age to women who did not have TNBC. We found that the women with TNBC in our cohort had elevated rates of BRCA2 mutations. We also found that women with a personal history of breast cancer were at risk for developing TNBC. This may be related to the use of hormonal therapy that reduces the risk of ER/PR-positive tumors. Women of all ages are at risk for developing TNBC and older age at TNBC should not deter from genetic testing.
Spatial distribution of veliparib measured by matrix-assisted laser desorption ionization mass spectrometry in triple-negative breast cancer tumors.
Authors: Bartelink Imke Heleen , Prideaux Brendan , Hann Byron , Krings Gregor , Coppe Jean-Philippe , Brown Swigart Lamorna , Lee Evelyn Pei Rong , Esserman Laura , Yee Douglas , Wolf Denise , Savic Rada M. 
Published: February 2017

161 Background: Veliparib is a potent inhibitor of the protein Poly(ADP-ribose) polymerase (PARP). Although effective, in the first clinical trials some TNBC patients fail to respond. We hypothesize that heterogeneous or insufficient drug concentrations in the solid tumor lead to inadequate response to PARPi in some TNBC patients. First we performed a mouse xenograft study to determine the penetration and distribution of veliparib in TNBC tumors in mice. Methods: MDA.MB.231 cells were injected bilaterally into mamamary fat pad of 10 Beige SCID mice. Veliparib (20mg/kg or 60mg/kg) or placebo was orally administered 3 times daily for 3 days. These doses and dosing schedules were estimated to result in equivalent plasma and tumor concentrations in mice compared to the doses currently used in clinical trials. Mice were euthanized 3 hours after the last dose of veliparib and tumors, liver and muscle tissues were obtained. In addition, control tissues were spiked with a broad range of concentrations of veliparib. The spatial distribution of the drugs in the tumor tissue was measured using Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI). The protonated molecular ion at m/z245.1 was used to construct 2D ion maps of the tissue showing relative quantitation of drug levels. HE staining was performed to characterize the tumors. Results: Veliparib in control tissues was detected at very low concentrations with a range of detection between 100 fmol-1nmol. After dosing, veliparib penetrates into the tumors and was detectable at both dose levels. However, drug distribution within the tumors was observed to be inhomogeneous. In spots where the drug accumulated, necrosis was observed. Conclusions: Veliparib can be measured using MALDI with good specificity and sensitivity and using concentrations equivalent to patients. TNBC tumors show largely heterogeneous distribution of PARPi. Future analyses will determine whether this heterogeneity in drug distribution explains variability in response to PARPi therapies.
Screening mammography rates in women with diabetes.
Authors: Tran Christine Wei-Yin , Wang Amy T. , Johnson Ryan , Ghosh Karthik , Shah Nilay 
Published: February 2017

25 Background: Women with diabetes are at an increased risk of developing breast cancer, present with later stage disease, and experience higher breast cancer-specific mortality compared to nondiabetic women. Thus, it is imperative that diabetic women undergo routine screening mammography. Previous studies have shown conflicting results with smaller studies showing lower screening mammography rates among diabetics while a study using national self-report data showed that diabetic women were equally likely to be screened compared to nondiabetic women. Given the conflicting data and limitations of previous studies, we aimed to study receipt of mammography in diabetic women using a nationally representative administrative claims database. Methods: This was a retrospective study using a nationally representative administrative claims database from January 1, 2010, through December 31, 2012. We compared rates of receipt of mammography within a 2-year time frame in diabetic and nondiabetic women ages 40 to 64. We used Healthcare Effectiveness Data and Information Set (HEDIS) logic to define women with diabetes. We used CPT and ICD-9 codes to identify mammogram services received. We calculated odds ratios with 95% confidence intervals to compare mammogram rates among diabetics compared to nondiabetics. Results: 1,723,674 nondiabetic women and 133,973 diabetic women were identified. Among women ages 40 to 49, diabetic women had significantly decreased mammography rates compared to nondiabetic women (OR 0.84; 95% CI 0.83, 0.85). Rates were also lower in diabetic women ages 50 to 64 (OR 0.88; 95% CI 0.88, 0.91). Despite lower mammography rates among diabetics, diabetic women had 1.78 times more visits than nondiabetic women. Conclusions: Women with diabetes are less likely to undergo routine screening mammography than women without diabetes, despite having more encounters with health care providers. This study serves as a reminder to provide timely preventive health services to all patients regardless of medical comorbidities.
Utility of Oncotype DX risk assessment in patients with invasive lobular carcinoma (ILC).
Authors: Tsai Michaela L. , Money Joel E , Finkelstein Marsha J , Lillemoe Tamera J , Susnik Barbara , Grimm Erin V , Kang Sung-hae L , Swenson Karen K 
Published: February 2017

28 Background: Oncotype DX (Genomic Health, Redwood City, CA) is a breast cancer assay that uses reverse transcriptase polymerase chain reaction (RT-PCR) to measure gene expression in paraffin-embedded tumor tissue, which correlates with recurrence risk. This test is used to guide chemotherapy decisions in patients with estrogen receptor-positive breast cancer. Invasive lobular carcinoma (ILC) is a distinct histologic subtype, inherently estrogen receptor rich, that has not been the unique focus of prior studies validating Oncotype DX. The study purpose was to determine if there are certain features of ILC that predict uniformly low Oncotype DX Recurrence Scores (RS) such that Oncotype DX testing may be unnecessary, saving patients time and financial resources. Methods: A search was conducted of all ILC cases having Oncotype DX testing in our hospital pathology database. The Oncotype DX RS, histologic tumor characteristics (including subtype and grade), immunohistochemical (IHC) analyses of estrogen receptor (ER)/progesterone receptor (PR) percent (by image analysis), E-cadherin expression, and Ki-67 levels were obtained for each case. Discriminant analysis was used to test the hypothesis that tumors classified as low or high risk based on the Oncotype DX RS would differ significantly on a linear combination of selected variables. Results: From 2006 to 2013, 158 cases of ILC having Oncotype DX testing were identified; 90 low risk (RS <18), 66 intermediate risk (RS 18 – 30) and 2 high risk (RS > 30). Discriminant analysis showed that PR% followed by Ki-67 provided the greatest contribution to discriminating between low versus high RS. A subset of 57 cases (~ 36%) with predicted probabilities > 86% for either low or high RS yielded 96.5% correct classification, 92.3% sensitivity, and 97.7% specificity. Conclusions: Our analytical model may be useful in predicting high versus low recurrence risk in some patients with ILC. If validated, this provides a faster and less expensive alternative to Oncotype DX testing in certain patients with ILC.
Chemosensitivity and endocrine sensitivity prediction by MammaPrint and BluePrint in the Neoadjuvant Breast Registry Symphony Trial (NBRST).
Authors: Whitworth Pat W. , Gittleman Mark , Akbari Stephanie , Stork Lisette , De Snoo Femke , Untch Sarah , Beitsch Peter D. 
Published: February 2017

29 Background: Classification into molecular subtypes is important for the selection of therapy for patients with breast cancer. Previous analyses demonstrated that breast cancer subtypes have distinct clinical outcome (Gluck, BCRT 2013). The aim of the prospective NBRST study is to measure chemosensitivity as defined by pathologic complete response (pCR), or endocrine sensitivity as defined by partial response (PR) and metastasis-free survival in molecular subgroups. Methods: The study includes women aged 18 to 90 with histologically proven breast cancer, who are scheduled to start neoadjuvant chemotherapy (NCT) or neoadjuvant endocrine therapy (NET), and who provide written informed consent. Additional inclusion criteria include no excision biopsy or axillary dissection, no confirmed distant metastatic disease, and no prior therapy for breast cancer. Treatment is at the discretion of the physician adhering to NCCN approved regimens. Results: Of 336 patients, T1-4 N0-3, had definitive surgery and the overall pCR rate was 24%. 32/167 (19%) IHC/FISH ERPR+/Her2- patients were reclassified by BluePrint (31 Basal). 43/95 (45%) IHC/FISH Her2+ patients were reclassified by BluePrint (25 Luminal and 18 Basal). 3/74 (3%) IHC/FISH triple-negative patients were not Basal by BluePrint. Of 45 (13%) patients classified as Luminal A 32 received NCT; one patient (3%) had a pCR; 13 patients received NET and 9 (70%) had a PR. Of 116 (35%) patients classified as Luminal B, 111 received NCT and seven (6%) had a pCR. The pCR rate (17/149 (11%)) in IHC/FISH ERPR+/HER2- patients was higher. Fifty-five (16%) are BluePrint HER2 and received NCT (51 plus trastuzumab); 27 (49%) had a pCR compared to 35/95 (37%) in IHC/FISH HER2+ patients. One-hundred twenty (36%) are BluePrint Basal and received NCT; 46 (38%) had a pCR, similar to the pCR percentage seen in the 74 patients designated triple-negative by IHC/FISH. Conclusions: Molecular subtyping using MammaPrint and BluePrint leads to a reclassification of 23% (78/336) of tumors. BluePrint reclassification resulted in better grouping of patients into expected response groups compared to local surrogate subtyping with immunostains.
Genomic profiling of early-onset and hereditary breast cancer.
Authors: Al-Mulla Fahd 
Published: February 2017

30 Background: Worldwide, breast cancer is the most common cancer in women. Susceptibility is thought to be polygenic and the risk tends to increase in women with positive family history of breast cancer. Methods: We proposed an ambitious Middle Eastern-based study that entailed exome sequencing of approximately 50 women from the Middle East (M.E) with moderate family history of any cancer. DNA from tumor samples with matching lymphocytes from the same subjects and 50 normal Middle Eastern women without history of familial or sporadic cancers in the family, were subjected to whole-exome sequencing on the HiSeq 1000/2000 Illumina platforms to map major breast cancer–activating genetic defects. Results: Several unique to the M.E region and novel germline mutations in non-BRCA1/2 genes were identified in this cohort. Germline mutations in TP-53, BARD1 and mismatch repair genes were more frequent than expected by chance. More importantly, the breast cancers showed interesting copy number and mutations variants that may aid our understanding of breast cancer initiations. Conclusions: The M.E. breat cancer may be caused by a unique set of germline variants and that the M.E breast cancers may represent an entity that may aid in our understanding of this common disease.
In vitro chemosensitivity testing of mammospheres cultured from circulating epithelial tumor cells (CETCs) of breast cancer patients: Comparision to chemosensitivity of total CETCs.
Authors: Pizon Monika , Zimon Dorothea , Pachmann Ulrich A. , Pachmann Katharina 
Published: February 2017

50 Background: In vitro chemosensitivity testing of circulating epithelial tumor cells (CETCs) provides real-time information about the sensitivity of the tumor cells present in the patient. Nevertheless, a fraction of CETCs can survive after conventional chemotherapy and grow into distant metastasis. This may be a subpopulation of CETCs with proliferation activity which has the ability to form floating spheres in suspension culture. Spheroids exhibit stem cell-like properties and may be responsible for chemotherapeutic resistance. Therefore, the aim of our study was to determine the efficacy of chemotherapeutics on spheroids cultured from CETCs. Methods: The enumeration of CETCs from patients with solid tumors in clinical stage I to IV was performed using the maintrac method. Subsequently, CETCs in the context of the surrounding white blood cells were cultured in a suspension culture allowing for spheroid formation. To evaluate the cytotoxic effect of drugs on CETCs and spheroids we exposed them to anticancer drugs in short time culture in different concentrations and for different periods of time. Results: In contrast to CETCs, spheroids were significantly more chemotherapy resistant. Active drugs led to disintegration of tumor spheres. Interestingly, some cells in the spheres were able to survive. Epirubicin and especially salinomycin, a polyether ionophore antibiotic isolated from Streptomyces albus, showed high efficacy in a high proportion of cells. Furthermore, our data suggested that curcumin, a natural biologically active compound that is extracted from the plant Curcuma longais a promising agent for cancer treatment. Docetaxel, cyclophosphamide, and 5-fluoruracil showed lower cytotoxic effects onto the cells in the spheres. Conclusions: Our results show, for the first time, that stem cells circulating in peripheral blood, capable of forming spheroids are way more resistant to anticancer drugs than the remnant circulating tumor cells. We, furthermore, demonstrate that salinomycin and curcumin efficiently destroy spheroids cultured from CETCs, strengthening their role as promising anticancer therapeutics.
Follow-up decisions and care after BRCA testing.
Authors: Assad Hadeel , Naseer Maliha , Ahsan Samira 
Published: February 2017

52 Background: Women with a deleterious mutation in BRCA 1/2 genes have an increased lifetime risk of developing breast and ovarian cancer. A spectrum of risk reducing and early detection strategies exist including clinical and radiographic surveillance, hormonal therapy, and prophylactic surgery. Methods: We studied the pattern of clinicopreventive inclination among patients undergoing BRCA testing in our genetics center via a telephone based questionnaire. Differences in sociodemographic and clinical characteristics were identified using independent sample t-test and Fisher exact test. Results: A total of 320 individuals were seen at the genetics center between October 2007 and February 2013. Twenty-nine were eligible of which 25 agreed to participate; 20 were found to be BRCA positive and 5 were true negatives. Most participants (> 75%) informed family members they were undergoing BRCA testing and all women shared the result of their deleterious mutation. An average of 2.2 (SD: 1.28) subsequent family members were tested which led to the discovery of 1.33 (SD: 1.15) new deleterious BRCA mutation carriers. Of the 20 BRCA positive patients, 13 opted for prophylactic surgery of which 5 underwent prophylactic oophorectomy (PO), 4 had prophylactic mastectomy (PM), and another 4 combined PO with PM. The remaining chose increased surveillance. Hormonal therapy was used as a preventive program in 6 women, 4 combined it with prophylactic surgery. Data subanalysis revealed BRCA carriers who opted for prophylactic surgery were more likely to be white (> 75%), younger, multiparous, live in Detroit suburbs, and have a personal history of cancer (92% versus 83%, respectively). Screening and surveillance practices were variable in timing and modality. Conclusions: 65 % of women with deleterious BRCA mutation underwent prophylactic surgery as their cancer risk reducing method. Decisions regarding adopting least to most aggressive measures remain highly influenced by personal history of cancer as well as individual socioeconomic characteristics. Understanding factors that affect women’s decisions to adopt various risk reduction strategies will aid both mutation carriers and clinicians to decide on optimal management.
Residual cancer found on re-excision for close and positive margins after breast conservation for early-stage breast cancer: A single-institution review.
Authors: Rice Dahlia Michelle , Ching Karen Beatrice Salud , Gambhir Sahil , Woo Edward 
Published: February 2017

55 Background: The SSO/ASTRO guidelines for margins on breast-conservation therapy (BCT) were recently published, recommending re-excision for positive margins only defined as ink on invasive cancer. The aim of our study is to retrospectively analyze our institution’s re-excision rate and the rate of finding residual cancer in the re-excision specimen when re-excisions were performed for positive and/or close margins. We want to confirm that our institution’s data for re-excision rates and residual cancer rates are comparable to national data from where the SSO/ASTRO guidelines were derived. Methods: A 3-year (2010 to 2012) retrospective review of data from our institution’s prospectively collected breast cancer database was performed for all stage 0, I, and II breast cancer patients who underwent BCT with subsequent re-excision or completion mastectomy for close or positive margins. Close margins were divided into two groups of < 1 mm or 1 to 2 mm margins, and positive margins were defined as tumor cells present on ink of specimen. Results: A total of 688 patients were analyzed. Our population was found to consist mostly of Caucasian females who were postmenopausal and married. 68% (468/688) of patients were found to have invasive ductal carcinoma (IDC), of which 27.8% (130/468) underwent re-excision for positive and/or close margins. Rates of residual cancer found in margins that are positive, < 1 mm, and 1-2 mm were 54.8% (17/31), 56% (14/25), and 6.3% (1/16) respectively. For DCIS, 38.9% (65/167) underwent re-excision. Rates of residual cancer found in margins that are positive, < 1 mm, and 1 to 2 mm were 38.9% (7/18), 28.6 % (4/14), and 20% (2/10) respectively. Conclusions: Our results reveal that in our institution, re-excision rates are comparable to published data. However, in patients with both positive and < 1 mm margins, the rates of finding residual cancer in the re-excision specimen was higher than the national average. Therefore, in our institution, further analysis is necessary prior to adopting the current recommended guidelines by SSO/ASTRO to prevent adverse impact in local recurrence rate.
Barriers to screening mammogram in southeastern Kentucky.
Authors: Elsoueidi Raymond , Adane Eyob , Richa Elie Maroun 
Published: February 2017

6 Background: Breast cancer is the most common cancer in females. Screening mammogram has been linked to reduced breast cancer mortality through early detection and effective treatment following diagnosis. Despite the dramatic improvement in the use of screening mammogram nationwide, disparities still exist. Southeastern Kentucky has multiple barriers to healthcare access with screening mammogram rates of around 63% compared to 80% in urban areas. We performed this observational study to identify the barriers to screening mammogram in southeastern Kentucky. Methods: Questionnaires were distributed to women age 40 and older at local churches and hospitals in 10 counties of southeastern Kentucky. Questions included age, healthcare coverage, having a primary care physician, having a mammogram within the past 2 years, and reasons for not having a mammogram. Results: Among the 328 females that participated in the survey, 36.3% did not have a mammogram. The median age (interquartile range) was 57 (50 to 63) and there were no difference between respondents with a mammogram and those without. Among the 119 females without a mammogram, the most common reasons for not having a mammogram were as follows: no interest in having a mammogram (33%), not being referred by their primary physician (24%), lack of time (12%), and lack of insurance (11%). Other responses included old age (5%), fear of pain of the procedure (3%), lack of knowledge/information (3%), and lack of transportation (2%). Seven percent did not provide reasons. Conclusions: Based on this survey, the most common barrier to obtaining a screening mammogram is patient perception, as evidenced by lack of interest, time, and knowledge/information, followed by failure of referral by physicians. Interventions that target these barriers will likely improve adherence to screening mammogram.