bluuebunny/crossref_metadata_2025 huggingface dataset:
HER2 amplification and overexpression between primary and liver metastatic breast cancer: Significance and implication.
Authors: Williams Casey B. , De Pradip , Klein Jessica , Williams Kirstin Anne , Cyr Brigitte , Small Misty , King Michelle , Carlson Jennifer , Sun Yuliang , Young Brandon Michael , Willis Scooter , Dey Nandini , Krie Amy K. , Leyland-Jones Brian
Published: February 2017

150

Background: The systemic management of metastatic breast cancer (MBC) is mostly based on the ER or HER2 status of the primary tumor. However, the hormonal status or the amplificaction/overexpression HER2 may change in every metastatic site because of the effects of the long-term treatment of metastatic cancer with endocrine therapy, chemotherapy, or targeted agents. The purpose of this study was to investigate the frequency of change in HER2 expression in primary and distant metastatic tumors (especially in liver) in HER2+ breast cancer patients. Methods: We retrospectively analyzed the results of 31 consecutive metastatic breast cancer patients that were seen in our center over 4 months from February 2014 through May 2014. All patients were rebiopsied after consultation and samples were sent for standard immunohistochemistry (IHC) for ER, PR, and HER2 and formalin-fixed, paraffin-embedded (FFPE) samples were sent for genomic (Foundation Medicine) and proteomic analysis (Theranostics). All results from the metastatic samples were compared to the baseline IHC and/or FISH results for HER2. Results: A change in HER2 status was observed in 26% of the cases. 16% of cases underwent a negative to positive conversion in HER2 status while 10% of cases underwent a positive to negative conversion. It is notable that all 5 patients that underwent a negative to positive conversion in HER2 status had biopsies taken from metastatic disease in the liver. Overall, 45% of patients with metastatic disease in the liver had a negative to positive conversion in HER2 status. Conclusions: The results of this study emphasize the significance of confirming HER2 expression in a recurrence lesion. This discordance may be due to the increasing level of genetic instability occurring throughout disease progression that can significantly influence the alterations of the HER2 gene. If feasible, HER2 reassessment in metastatic lesions should be carefully taken into account, especially for metastases coming from non-HER2 amplified breast cancer. Although HER2 status is usually appraised in primary tumor, knowledge of the HER2 status in metastases may be of potential value for therapeutic decision making.
The basal phenotype as a clinically relevant indicator of trastuzumab resistance in HER2+ breast cancer.
Authors: Choi Michael Phillip , Chung Alice P. , Bose Shikha , Han Bingchen , Qu Ying , Zhang Xiao , Cui Xiaojiang , Giuliano Armando E.
Published: February 2017

154

Background: Trastuzumab (Herceptin) resistance remains a clinical challenge but the mechanism is not well understood. Recently, studies have identified a subset of Her2+ breast cancer called basal HER2 that expresses basal genes. We investigated the effect of basal gene expression on Herceptin response in HER2+ breast cancer cell lines and on prognosis in HER2+ breast cancer patients. Methods: Non-basal (BT474, SKBR3) and basal (HCC1569, HCC1954, JIMT-1) HER2+ cell lines were chosen based on basal cytokeratin expression. Cell proliferation was assessed after treatment with vehicle, Herceptin (H), Paclitaxel (P), H+P, Akt Inhibitor (AI), and H+AI. HER2 signaling was examined using immunoblotting of p-Akt and p-ERK. Because breast cancer stem cells (BCSC) are linked to basal breast tumors and treatment resistance, we assessed BCSC activity using mammosphere formation and aldehyde dehydrogenase (ALDH) positivity. Immunohistochemical staining of HER2+ breast cancers for basal markers CK5/6, CK14, and EGFR was correlated with clinicopathologic features and survival in 88 patients with Stage 1-3 HER2+ breast cancer treated with Herceptin. Results: Basal HER2 cells were resistant to Herceptin compared to non-basal HER2 cells but this resistance was overcome by Akt inhibition. Immunoblotting showed that non-basal HER2 cells had decreased p-Akt after Herceptin treatment which was not seen in basal HER2 cells. There was no difference in p-ERK levels after Herceptin therapy in all cell lines. Basal HER2 cells had increased mammosphere formation and ALDH positivity suggesting higher stem cell activity compared to non-basal HER2 cells. Of the HER2+ patients, 33/88 (37.5%) expressed at least one basal marker. Basal Her2 tumors were associated with higher grade (p = 0.04) and more ER/PR negativity (p < 0.01). CK14 expression correlated with worse overall survival by log-rank test (p = 0.02), while EGFR showed a similar trend (p = 0.06). Conclusions: Basal HER2 breast cancer cell lines have Herceptin resistance which may be due to constitutively active Akt signaling and increased stem cell activity. Clinically, basal marker expression predicts Herceptin resistance and worse outcomes in HER2+ breast cancer patients.
Incidence of germline BRCA mutation in patients with ER-low positive/PR negative/HER-2 neu negative tumors.
Authors: Sanford Rachel Ann , Song Juhee , Gutierrez-Barrera Angelica M. , Litton Jennifer Keating , Bedrosian Isabelle , Albarracin Constance T. , Valero Vicente , Arun Banu
Published: February 2017

2

Background: The 2011 ASCO/CAP guidelines recommend that breast cancers with estrogen receptor (ER) staining as low as 1% on immunohistochemistry be considered ER-positive. In practice, there remains significant variability in what clinicians consider ER-positive versus ER-negative. Current NCCN guidelines recommend that patients under age 60 with triple-negative breast cancer (TNBC) be referred for genetic counseling and consideration of germline BRCA mutation testing. With the 2011 ASCO/CAP guidelines, the definition of TNBC has changed to exclude patients with ER low-positive (1-9%) tumors; hence patients with ER-low positive tumors (formerly considered ER negative) may not be referred for genetic counseling and BRCA testing. This may lead to “undertesting” of appropriate patients. The incidence of BRCA germline mutations in patients with ER-low positive versus ER-negative (0%) tumors is unknown. We sought to identify whether the incidence of BRCA mutation differed between patients with ER-negative/PR-negative/HER-2 neu negative tumors and patients with ER-low positive/PR-negative/HER-2 neu negative tumors. Methods: We performed a review of a prospectively maintained research database of all patients with ER < 10%, PR 0% and HER-2 neu–negative breast cancers who were referred for genetic risk assessment and testing for BRCA mutation at UT MD Anderson Cancer Center. Results: Of 144 patients who underwent BRCA mutation testing, 22 (15%) had ER-low positive tumors while 122 (85%) had ER-negative tumors. Among patients with ER-low positive tumors, 7 of 22 (31.8%) were found to have a deleterious BRCA 1/2 mutation, while 33 of 122 (27%) with ER-negative tumors were found to have a deleterious BRCA 1/2 mutation. The incidence of deleterious BRCA 1/2 mutation in patients with ER-low positive tumors versus those with ER-negative tumors was not statistically significantly different (p = 0.6457). Conclusions: The rate of deleterious BRCA 1/2 germline mutations in ER-negative versus ER-low positive (1-9%) breast cancer is similar. Therefore, we strongly recommend that BRCA testing continue to be offered to women under age 60 with tumors that are ER-low positive/PR-negative/HER-2 neu negative.
Use of serum biomarkers to differentiate benign breast lesions from invasive breast cancer in women with a BI-RADS 3 or 4.
Authors: Henderson Meredith C. , Silver Michael , Yeh Susan , Corn Christa , Borman Sherri , Reese David Emery
Published: February 2017

20

Background: The Provista Biomarker Assay (PBA) combines multiple serum biomarkers, measured at high sensitivity, in order to determine the likelihood of an invasive breast tumor at the time of testing. PBA, when paired with traditional breast imaging technologies, provides a biochemical tool that can help guide additional imaging or biopsy decisions. As part of our ongoing efforts to characterize clinical performance, we conducted a proof-of-concept study wherein PBA assay performance was tested in prospectively enrolled BI-RADS 3 and 4 patients. Methods: To maximize performance and sensitivity, we utilized the Meso Scale Discovery ELISA-based system to analyze a randomized cohort of 350 prebiopsy serum samples from women under the age of 50. Enrollment in the trial required a BI-RADS 3 or 4 radiologic assessment utilizing multiple imaging modalities. Serum proteins and autoantibodies were measured for each patient and applied to a proprietary statistical algorithm. Results: We were able to obtain statistically significant differentiation using the Provista Biomarker Assay in women under age 50 who were characterized as BI-RADS 3 or 4. The majority of patients in the study were diagnosed with a benign breast lesion, consistent with prior studies. However, the data indicate that PBA, when used in combination with imaging techniques, more accurately informs clinical decision-making. Conclusions: The Provista Biomarker Assay provides a powerful tool for physicians to more accurately assess patients with a BI-RADS 3 or 4 classification. With more clinical evidence, the assay may translate into changes in clinical treatment decisions for women under the age of 50 with a BI-RADS 3 or 4 classification. Clinical trial information: NCT01839045.
Next-generation sequencing for inherited cancer risk assessment: Under the hood at Counsyl.
Authors: Maguire Jared Robert
Published: February 2017

22

Background: Next-generation DNA sequencing (NGS) is the universal nucleic acid assay technology, with the capability to replace nearly all existing DNA assay technologies. In most cases it is more affordable, more accurate, more flexible, and less subject to human error than prior assay technologies such as capillary electrophoresis or genotyping arrays. In the last year especially, NGS utilization in the clinic has increased. The use of NGS to detect single nucleotide polymorphisms (SNPs) and short insertions/deletions (indels) is well established. However, primarily due to novelty, NGS for has not yet often been used in the clinic for the detection of larger copy number variants (CNVs). Instead, supplementary technologies such as multiplex ligation-probe amplification (MLPA) and quantitative PCR (qPCR) have been used to probe large CNVs. Methods: Counsyl’s Family Prep and Inherited Cancer Screens use NGS for detecting SNPs and indels, and also CNV analysis in the genes of interest. Here we present the technical details of the platform and our validation results showing that CNV analysis by NGS meets or exceeds the performance of such analysis by MLPA or endpoint TaqMan. Only two discordant CNV genotypes were found out of 20,086 calls; both discordances are errors in the control assay, and are attributable to technical limitations. Results: See Table. Conclusions: CNVs account for a significant proportion of BRCA1 and BRCA2 associated cancer risk. Our NGS methodology achieves analytical performance previously obtained only by multiple assays, decreasing testing costs and thereby potentially widening access. [Table: see text]
Association of single-nucleotide polymorphisms of USP7 gene with breast cancer suscepbility in Chinese women.
Authors: Jiang Huangang , Zhou Fuxiang , Wang You , Wei Yuehua , Xu Hui , Hu Liu , Wang Wenbo , Zhao Hong
Published: February 2017

27

Background: The tumor suppressor p53 pathway plays a crucial role in preventing carcinogenesis. It was reported that activity of p53 was regulated by USP7 (Ubiquitin Specific Peptidase 7) and TSPYL5 (Testis-specific Y-encoded-like protein 5). This study was carried out to assess the association between single nucleotide polymorphisms (SNPs) in P53, USP7, TSPYL5 genes and the breast cancer susceptibility in Chinese Han women. Methods: DNA was extracted from the peripheral blood samples of breast cancer patients and age-matched controls. In the first stage, tag SNPs of P53, USP7, and TSPYL5 genes were selected with Hapmap database and Haploview program. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay was used for genotyping. Then, two positive SNPs were determined by polymerase chain reaction- restricted fragment length polymorphisms assay (PCR-RFLP) in the second stage. The ethics committee of Zhongnan Hospital of Wuhan University authorized this study. Results: In the first stage, 23 SNPs were selected and detected in 192 cases and 192 controls. The results demonstrated that the distribution of genotype of rs12924995, rs2304467 in USP7 gene was different in cases and controls (p = 0.026, 0.037, respectively). In the second stage, these two SNPs were determined. A total of 975 cases and 910 controls enrolled in the present study. Hardy-Weinberg equilibrium of rs2304467 and rs12924995 in the control group was tested (p = 0.979, 0.111). Multivariate analysis showed that breast cancer risk of women with C allele (CC or CG genotype) increased (p < 0.001, odds ratio = 1.87, 95% confidence interval, 1.44-2.44), compared with rs2304467 GG carriers. Besides, women with rs12924995A allele (AA or AC genotype) had higher risk of breast cancer than those with CC genotype (P=0.002, odds ratio=1.36, 95% confidence interval, 1.21-1.65). Breast cancer risk of women carried rs2304467C allele and rs12924995A allele also increased (p < 0.001, odds ratio = 2.05, 95% confidence interval, 1.54-2.73). Conclusions: SNPs rs2304467 and rs12924995 in USP7 gene are associated with breast cancer susceptibility in Chinese Han women.
Race, Oncotype DX, and other characteristics in a highly screened population.
Authors: Chun Jennifer , Schnabel Freya Ruth , Schwartz Shira , Billig Jessica , Kern Elizabeth , Hiotis Karen , Axelrod Deborah M. , Guth Amber
Published: February 2017

32

Background: Oncotype DX breast cancer 21 gene assay recurrence score (RS) is used to predict disease recurrence and response to chemotherapy in order to offer patients the highest treatment benefit to risk ratio. There is a dearth of literature on the relationship of Oncotype RS and race in women with hormone receptor positive and node negative/positive disease. The purpose of this study was to investigate the relationship of race and clinical characteristics (including Oncotype RS) in an insured population of highly screened women with newly diagnosed breast cancer. Methods: The Breast Cancer Database of our institution was queried for patients who were newly diagnosed with breast cancer. We looked at demographics, risk factors, tumor characteristics, and Oncotype RS. Statistical analyses included Pearson’s Chi-Square and Fisher’s Exact Tests. Results: A total of 1,767 women were diagnosed with breast cancer from 1/2010 to 4/2014. The median age was 59 years. There was a total of 1327 (75%) Whites, 162 (9%) Blacks, 163 (9%) Asians, and 108 (6%) Hispanics. Majority of patients had a college-level education (83%), had annual/biannual screening mammography (78%), and clinical breast exams (89%). Majority of patients had invasive ductal carcinoma (61%), early stage (0, I, II) tumors (94%), ER+ (85%), PR+ (72%), Her2-negative (86%), and node-negative disease (80%). Compared to Whites, there was a significantly higher proportion of later stage disease among Blacks (p = 0.001) and Asians (p = 0.003), more triple negative breast cancers among Blacks (p < 0.0001) and higher Ki-67 scores among Blacks (p < 0.001) and Asians (p < 0.001). Oncotype RS was not significantly different among the race categories and a majority of patients had a low Oncotype RS (57%). These results did not change after stratifying for nodal status. Conclusions: In a population of women who had health insurance and were highly screened, we found clinical differences among races with respect to tumor histology. However, we did not find a statistically significant difference among race and Oncotype RS, even after stratifying for nodal status. Further studies are warranted to determine which tumor proliferation markers are contributing to ethnic differences in breast cancer mortality.
Surgical outcome of lobular neoplasia diagnosed in core biopsy: Prospective study of 316 cases.
Authors: Susnik Barbara , Day Deborah , Krueger Janet , Abeln Ellen , Bowman Tara , Lillemoe Tamera J
Published: February 2017

4

Background: Recommendations for management of lobular neoplasia (LN) including lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia (ALH) diagnosed in core biopsy specimens (CB) are controversial. The aim of our prospective study is to identify subset of patients with LN diagnosed in CB who do not require subsequent surgical excision (SE). Methods: All patients with a diagnosis of ALH or LCIS on CB were referred for SE. Cases with coexistent DCIS or invasive breast carcinoma were excluded. Cases with coexistent ductal atypia including FEA or ADH (LN-DA) and LCIS variants including pleomorphic or necrotic LCIS (LN-V) were separated from classic LN (LN-C). Dedicated breast pathologists and radiologists reviewed all cases with careful imaging/pathology (IP) correlation. Results: From June 2008 to December 2013, 13,772 percutaneous breast CB procedures were performed. A total of 370 patients with LN diagnosed on CB were referred to SE. 302 (82%) patients with 316 lesions underwent SE within 2 months after initial diagnosis. Average age was 55.3, 27% had positive family history and 4% had previous breast carcinoma. After patients with synchronous ipsilateral CB showing cancer were excluded (20 patients) from upgrade analysis, the diagnostic groups included 228 LN-C, 15 LN-V and 53 LN-DA. In the LN-C group I/P discordance represented 6/228 cases (2.6%). Upgrade to carcinoma of LN-C varied between discordant (6/6) and concordant cases (8/222=3.6%). In comparison, upgrades were seen in 26.7% LN-V (4/15), and 28.3% LN-DA (15/53). For concordant LN-C, the imaging target was calcifications in 176/222 cases (81%); 7 were associated with upgrade (3.9%). Upgrades were rare for MRI targeted lesions (0/14) and mass lesions (1/32). Overall, upgrades were similar for ALH and LCIS (3.4% vs. 4.5 %). Conclusions: While LN with nonclassic morphology or with associated ductal atypia requires SE, this can be avoided in classic LN diagnosed on CB targeting calcifications when careful imaging/pathology correlation is applied; the likelihood of unsuspected cancer diagnosis is minimal and limited to coincidental cases. Until larger numbers are studied, excising classic LN diagnosed as masses or MRI detected lesions may be prudent.
Axillary ultrasonographic criteria to predict chemotherapy response in breast cancer patients receiving neoadjuvant chemotherapy.
Authors: Yoo Koun Joy , Kim Sun Mi , Kim Sung-Won , Park So Yeon , Choi Seung-Hee , Lee Jieun , Jang Mi Jung , Yun Bo La
Published: February 2017

48

Background: The purpose of the study is to evaluate ultrasonographic criteria to predict response of axillary LNs in patients with breast cancer receiving neoadjuvant chemotherapy. Methods: We retrospectively reviewed data of 402 patients who underwent neoadjuvant chemotherapy from August 2003 to December 2012. Of these, 202 breast cancers in 199 patients (bilateral in 2 patients) in whom axillary LN metastasis was confirmed using axillary ultrasonography (US) and US-guided fine-needle aspiration biopsy (FNAB) were included in the study. US evaluation was done for the long and short axes, and cortical thickening before and after chemotherapy. The ratio of decreased long and short axes and cortical thickening on prechemotherapy US was also calculated. Statistical analysis with receiver operating characteristic (ROC) curve was used to determine the valuable ultrasonographic criteria for predicting pathologic complete remission (CR) using Medicalc program. Results: Final pathologic diagnoses of LNs were yNo in 57, yN1 in 76, yN2 in 50 and yN3 in 19 cases. The mean size of LNs were 1.8cm in long axis, 1.0cm in short axis and 0.9cm in cortical thickening on prechemotherapy US and 1.1cm in long axis, 0.6 cm in short axis and 0.4 cm in cortical thickening on postchemotherapy US. The area under the ROC curve (AUC) was 0.578 for cortex thickening, 0.523 for the long axis, and 0.523 for the short axis of LN on postchemotherapy US. The AUC was 0.643 for the decreased cortex thickening ratio, 0.585 for the long axis ratio, and 0.585 for the short axis ratio. The most significant criteria was decreased cortex thickening ratio to the long and short axes (p < 0.05). The sensitivity and specificity of the decreased cortex thickening ratio for predicting CR were 43.7% and 80.7%, respectively, with a 0.5 cut off value. Conclusions: The most significant criteria for predicting CR was decreased cortex thickening ratio to the long and short axes. It is applicable for selecting sentinel LN biopsy candidates from among breast cancer patients who have undergone neoadjuvant therapy.
Increasing participation in breast cancer research: (INSPIRE-BrC).
Authors: Robinson Brandi , Swain Sandra M.
Published: February 2017

53

Background: Increasing black patients’ participation in cancer clinical trials is particularly important because of the population’s lower survival rate. Accrual to clinical trials remains low among the general population (1 to 3%), with recruitment of blacks the lowest of all groups at 0.5 to 1.5%. Clinical trials are key to developing new methods to prevent, detect, and treat cancer. INSPIRE-BrC aims to increase trial participation rates among black patients with breast cancer and examine the relationship between the intervention and attitudes/beliefs on the decision to participate. Methods: A sample size of 123 black patients with breast cancer at five MedStar sites will view a 15 minute, culturally tailored video about clinical trials, which targets six cultural and attitudinal barriers to participation. A pre-test/post-test method is used to determine the impact of the video on three variables — likely participation in therapeutic clinical trials; attitudes toward therapeutic clinical trials (assessed based on the 6 barriers); and actual trial enrollment. Expected Findings: We hypothesize that the intervention will increase clinical trial enrollment compared to our 2012 clinical trial enrollment baseline rate of 6% (22/384) for black patients with breast cancer in five MedStar hospitals. The primary outcome measure is the proportion of black patients with breast cancer who agree to participate in a therapeutic clinical trial among those who sign consent to INSPIRE-BrC. Study findings have the potential to increase patient recruitment as a promising tool for rapid dissemination of a theory-driven, evidence-based model to enhance clinical trial accrual among black patients with cancer. [Table: see text]
Racial/ethnic disparities in estrogen and progesterone receptor phenotype and survival outcomes.
Authors: Shameem Raji , Hamid Muhammad S , Sonpal Niket , Pudusseri Anita , Graham Robert , Sullivan Kevin M.
Published: February 2017

54

Background: The incidence of estrogen receptor (ER) and progesterone receptor (PR) phenotypes varies among different racial/ethnic groups. However, the prognostic significance of specific ER/PR phenotypes on survival in racial/ethnic groups including Asians has not been reported. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to identify invasive breast cancer cases from 1988 to 2009. Groups included were: “Non-Hispanic Whites (NHW)”, “Blacks”, “Filipinos”, “Chinese”, “Japanese”, “Koreans”, “Vietnamese”, and “Asian Indian/Pakistanis (AIP)”. Cases were grouped according to ER/PR phenotype (ER+/PR+, ER-/PR-, ER+/PR-, ER-/PR+). The Kruskall-Wallis test, and the Z test were employed to examine for differences between racial/ethnic groups. Multivariate Cox proportional analyses were used to establish the weight of the age adjusted ER/PR phenotype on the prognostic significance contributing to survival. Results: In comparison to NHW, ER+/PR+ status was associated with poor outcomes in blacks (HR: 1.814, p < 0.01), however improved outcomes were seen in Chinese (HR: 0.759, p <0.01), Vietnamese (HR: 0.755, p < 0.01), AIP (HR: 0.751; p < 0.01), Koreans (HR: 0.661, p < 0.01) and Japanese (HR: 0.608, p < 0.01). ER-/PR- status also was associated with decreased survival in blacks (HR: 1.391, p < 0.01), but improved survival in Chinese (HR: 0.793, p < 0.01), Filipinos (HR: 0.787, p < 0.01), Japanese (HR: 0.757, p <0.01), AIP (HR: 0.751, p < 0.01), Vietnamese (HR: 0.736, p < 0.01), and Koreans (HR: 0.705, p < 0.01). Compared to the referent NHW, ER+/PR- status in Chinese (HR: 0.765, p < 0.01), Japanese (HR: 0.794, p < 0.01), Filipinos (HR: 0.711, p < 0.01), and Koreans (HR: 0.662, p < 0.05) there was improved survival, while blacks (HR: 1.612, p < 0.01) had decreased survival. Regarding ER-/PR+ status, blacks (HR: 1.464, p < 0.01) had decrease survival, while only Japanese women exhibited improved outcomes (HR: 0.586, p < 0.01) compared to NHW. Conclusions: For ER/PR phenotypes including ER-/PR- tumors, Asian subgroups showed favorable survival outcomes compared to NHW, while poor outcomes were seen in blacks.
Effect of hormone receptor status and local treatment on overall survival for early-stage breast cancer.
Authors: Parker Catherine , Lin Heather Y. , Shen Yu , Li Liang , Lautner Meeghan Ann , Kuerer Henry Mark , Shaitelman Simona Flora , Babiera Gildy , Bedrosian Isabelle
Published: February 2017

60

Background: Mastectomy and breast conserving therapy (BCT) have been established as interventions with equivalent survival for early stage breast cancer. However, trials comparing these approaches pre-date the understanding of breast cancer heterogeneity. We hypothesized that if heterogeneity is considered, the surgical approach may impact survival. Methods: Using the National Cancer Database (NCDB) from 2004 to 2005, we evaluated the overall survival (OS) of women with Stage I breast cancer who underwent mastectomy, BCT (surgery with radiation), or breast conserving surgery (BCS, surgery without radiation). Since only ER and PR data were available, we categorized tumors as ER and/or PR positive (HR+) or ER and PR negative (HR-). We performed propensity score-matched analysis using the covariates associated with the choice of surgical therapy. We used the Cox proportional hazards model for analyses of OS in pre-matched and matched cohorts. Double robust estimation under the Cox model was used in the analyses of the matched cohort. Results: A total of 16,646 female patients met study criteria: 1,845 (11%) received BCS, 11,214 (67%) received BCT, and 3,587 (22%) underwent mastectomy. Patients undergoing BCT had superior survival outcomes compared to those undergoing mastectomy or BCS (5-year OS was 96% vs 90% vs 87% respectively, p<0.001). After adjusting for other risk factors, BCT remained significantly associated with OS (HR 0.57 [95% CI 0.50, 0.66] for BCT vs BCS; HR 0.67 [95% CI 0.6, 0.76] for BCT vs mastectomy). In the matched cohort (1706 patients in each treatment group), comparison of OS in multivariate analysis confirmed the survival benefit associated with BCT over mastectomy (HR 0.73 [95% CI, 0.59, 0.89]) in the HR+ subset but not in the HR- subset (HR 0.91 [95%CI 0.62, 1.34]) of patients. BCT showed better OS than BCS in both HR+ and HR- subsets (HR 0.63 [95% CI, 0.52, 0.77], HR 0.67 [95%CI 0.46, 0.98] respectively). No differences were seen in OS between mastectomy and BCS in either HR+ or HR- cohorts (HR 0.87 [95%CI. 0.73, 1.03]), HR 0.73 [95%CI 0.51, 1.06] respectively). Conclusions: When tumor heterogeneity is considered, type of local therapy appears to impact the survival of women with Stage I breast cancer.
Outcomes after local recurrence following breast-conserving therapy for early-stage breast cancer.
Authors: Jawad Maha Saada , Wobb Jessica , Wallace Michelle , Grills Inga S. , Pietron Arielle , Marvin Kimberly , Dilworth Joshua T. , Chen Peter Y.
Published: February 2017

66

Background: Limited data exist for patients who develop local recurrence (LR) following breast conserving therapy (BCT) for early stage breast cancer (ESBC). This study is to evaluate outcomes and predictors of failure following LR in patients treated with BCT. Methods: 1,654 women with ESBC underwent BCT from 1980 – 2013 at a single institution. All patients had breast-conserving surgery followed by whole breast irradiation (WBI) or accelerated partial breast irradiation (APBI). Subset analysis was performed for patients who developed LR as a first event. Clinical outcomes analyzed include contralateral breast failure (CLBF), regional recurrence (RR), distant metastases (DM), cause-specific survival (CSS), and overall survival (OS). Continuous variables were analyzed with an independent samples t-test and categorical variables with χ2. Univariate analysis was performed to determine factors predictive for events after LR. Results: 112 (7%) patients developed LR (87 WBI; 25 APBI), with median time to LR of 6.6 yrs (0.1-28). Median follow-up for the LR group was 14 yrs (0.7-31) overall; 10 (0.7-19) and 16 yrs (1.4-31) for APBI and WBI, respectively (p=0.01). A change from initial to LR pathology was seen for: ER status 21%, PR status 25%, HER2 status 13%, grade 38%, histology 40%, and LVSI 38%. Salvage treatment following LR was mastectomy ± chemotherapy (CHT) in 75%, wide local excision ± RT in 19%, CHT in 2%, and other in 4%. Outcomes following salvage treatment for LR are shown in the table. No differences were seen in outcomes between patients treated with APBI v WBI. Univariate analysis failed to demonstrate any factors predictive for events following LR. Conclusions: Patients who developed LR following BCT for ESBC had excellent clinical outcomes at 5 and 10 yrs, demonstrating effective salvage treatment in this cohort of patients. No differences were noted between patients undergoing APBI v WBI. Further identification of histopathologic patterns between first cancer and LR is currently underway. [Table: see text]
A phase II trial of once-weekly hypofractionated breast irradiation (WHBI): Interim analysis of cosmetic outcome and quality of life.
Authors: Dragun Anthony E. , Riley Elizabeth Carloss , Quillo Amy R. , Barry Parul Nafees , Hunter Allison M. , Rajeurs Akanksha A. , Roberts Teresa , Rai Shesh , Pan Jianmin , Jain Dharamvir , Scoggins Charles Raben , McMasters Kelly
Published: February 2017

67

Background: A planned interim analysis of an institutional Phase II trial of once-weekly radiotherapy for patients undergoing breast-conserving surgery (BCS). Methods: Patients who underwent BCS for AJCC Stage 0, I or II breast cancer with negative surgical margins were eligible to receive whole-breast radiotherapy to a dose of 30Gy in 5 weekly fractions of 6 Gy with or without an additional boost. There were no restrictions on age, breast size or the use of cytotoxic chemotherapy for otherwise eligible patients. Patients were evaluated at baseline, 6 and 12 months with digital photography, physician assessment of cosmesis (Harvard Scale) and self-assessment (BCTOS). Results: Between January 2011 and January 2013, 82 eligible patients underwent WHBI immediately following BCS (82.7%) or at the conclusion of adjuvant cytotoxic chemotherapy (17.3%). The median age was 60 years (range: 30-80y) and the median followup was 33.1 months and all patients had at least 1 year followup. The rate of Excellent/Good vs. Fair/Poor cosmesis at 12 months was 77.3% vs. 22.7%. The rate of significant cosmetic change from baseline was 14.7%. The only factor predictive of significant cosmetic change was smoking status (OR: 6.94; p = 0.016). The median BCTOS score increased only slightly from baseline (31) to one year (32), with patient-reported breast size differences worsening but complaints of pain improving over the study period. Conclusions: Cosmetic outcome after WHBI compares well with reports of daily hypofractionated whole-breast irradiation. Further follow-up with continued accrual is needed to assess cosmetic stability and disease-specific outcomes. Clinical trial information: NCT01278212.
SPIO-enhanced MR imaging at 3T for accurate diagnosis of sentinel node metastases to avoid sentinel node biopsy in patients with breast cancer.
Authors: Motomura Kazuyoshi , Nakayama Takahiro , Tamaki Yasuhiro , Ito Yuri , Nakanishi Katsuyuki
Published: February 2017

68

Background: We previously demonstrated the usefulness of SPIO-enhanced MR imaging at 1.5T for the detection of metastases in sentinel nodes identified by computed tomography lymphography (CT-LG) in patients with breast cancer (Ann Surg Oncol 2011, ASCO 2012). The aim of this study was to evaluate whether SPIO-enhanced MR imaging at 3T improved the diagnostic accuracy for the detection of metastases in sentinel nodes. Moreover, these results were compared with those of the diagnosis using CT-LG according to the size criteria. Methods: Seventy patients with breast cancer and clinically negative nodes were included. Sentinel nodes identified by CT-LG were evaluated prospectively using SPIO-enhanced MR imaging at 3T. Sentinel node size was measured on CT-LG and a node larger than 5 mm in short axis diameter was considered metastatic. Sentinel nodes localized by CT-LG were removed, and imaging results and histopathological findings were compared. Results: The mean patient age was 55 years (range, 29-78). Sentinel nodes were identified by CT-LG successfully in 69 (98.6%) of 70 patients. The mean number of sentinel nodes identified by CT-LG was 1.4 (range, 1-3). All 19 patients with positive sentinel nodes definitively diagnosed by pathology demonstrated metastases on SPIO-enhanced MR imaging. Forty-eight of 50 patients with negative sentinel nodes definitively diagnosed by pathology were non-metastatic on the imaging studies. The sensitivity, specificity and accuracy of MR imaging for the diagnosis of sentinel node metastases were 100%, 96.0%, and 97.1%, respectively, on a patient-by-patient basis. Those of CT-LG were 78.9%, 56.0%, 62.3%, respectively. The specificity and accuracy of MR imaging were superior to those of CT-LG (McNemar test; p < .0001 and = .0015, respectively). Conclusions: SPIO-enhanced MR imaging at 3T can accurately diagnose the sentinel node metastases, and therefore sentinel node biopsy may not be required for most patients with breast cancer.
Clinical efficacy of accelerated partial-breast irradiation in treatment of ER-negative breast cancer: Results of a matched pair analysis.
Authors: Chen Peter Y. , Wobb Jessica , Wallace Michelle , Grills Inga S. , Jawad Maha Saada , Pietron Arielle , Dilworth Joshua T. , Dekhne Nayana , Brabbins Donald S.
Published: February 2017

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Background: To assess outcomes of ER-negative breast CA pts treated with APBI, a matched-pair analysis was performed to determine efficacy of APBI vs whole breast RT (WBRT) from a single institution. Methods: From over 1650 pts treated with BCT from 1980-2013, a cohort of ER[-] pts treated with APBI or WBRT were investigated. Matched-pair analysis with a 1:1 ratio paired 79 APBI with 79 WBRT pts, all ER[-] (total:158). Match criteria included follow-up (FU) > 1.0 yr, stage, & age +/- 5 yrs. Outcomes analyzed included local recurrence (LR), true recurrence/marginal miss (TRMM), regional recurrence (RR), distant metastases (DM), disease-free (DFS), cause-specific (CSS), and overall survivals (OS). Results: As for clinical-pathological traits, no significant differences were noted for age (p=0.302), T-stage (p=1.000), tumor size (p=0.721), N-stage (p=0.062), use of chemoRx (p=0.747), endocrine Rx(p=0.408) or Herceptin (p=1.00). Per ASTRO Guidelines, no differences were seen in cautionary or unsuitable [UnS] groups between APBI & WBRT (p=0.333). With a mean FU of 8.0 yrs (10.1 yrs APBI; 8.4 yrs WBRT p<0.001), no differences were seen in the 10-yr actuarial rates of LR (9.3% vs 22.1% p=0.094), RR (1.3% vs 8.1% p=0.299), DM (7.1% vs 13.0% p=0.429), DFS (83.9% vs. 72.5% p=0.214), CSS (93.5% vs. 89.0 % p=0.677), or OS (79.6% vs. 80.1% p=0.573) between APBI & WBRT. Only TRMM was significantly different (0% APBI vs 12.5% p=0.011). In stratifying patients based on ER% (0%, 1-3%, 4-8%) no outcome differences were noted. Of the 158 ER[-] pts, 124 were cautionary with similar 10-yr outcomes except for TRMM (0% APBI;WBRT 14.4% p=0.017) & CLBF (0% APBI;WBRT17.1% p=0.019). For the 34 UnS patients, no endpoint differences were seen APBI vs WBRT. But, when the entire 158 ER[-] patients were analyzed for # of UnS factors, increasing UnS factors led to significant risk of RR (p<0.001) & DM (p=0.002). Conclusions: With 10-year FU of APBI for ER[-], the clinical results were equivalent to WBRT. No differences were noted based on ER%. Increasing number of unsuitable factors had more RR and DM. Maturation of randomized trial data will be needed to provide Class I evidence for equivalence of APBI to WBRT in ER[-] patients.
Utilization of breast preservation treatments in Hispanic patients with breast cancer: An analysis from the National Cancer Data Base (NCDB) from 2000 to 2011.
Authors: Martinez Alvaro , Arrojo Elisabeth E. , Vicini Frank A.
Published: February 2017

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Background: In contrast to mastectomy, radiotherapy (RT) treatments for breast cancer (BC) patients, allows for the benefits of breast preservation therapy and brachytherapy (BT) is a very convenient and short course of RT. BT use in BC has increased since FDA approval in 2002, however, has it been used evenly among races? Methods: Trends of treatment were analyzed for BC patients stages Tis to IV using the NCDB and 2.015.671 cases were found. Specific analysis of treatment differences between Black, White and Hispanic races, and the use of BT was performed. Results: The use of surgery as the only treatment in BC patients has decreased in stages 0 to IV (-7%, -11%, -8%, -6% and -6%; p<0.0001), while the use of RT has increased in stages 0 to III (+5%, +1%, +3%, +8%; p<0.0001). The use of chemotherapy has also increased in stages 0, I, III, IV (+3%, +4%, +7%, +5%; p<0.0001), while decreased in stage II (-3%; p<0.0001). Hispanic patients, received less RT in stages I to III (-4.11%, -5.46%, -4.84%; p<0.05), while White’s in stage I and III (58.11%, 65.98%), and Black’s in stage II (52.19%) received more RT (p<0.05). In addition, Hispanic’s received significantly more mastectomy in stages I, II and IV. BT as a type of RT was used mainly in stages 0 to II. In stages III and IV its use was <0.13%. 50.836 patients stage 0-II received BT. In this group of patients, BT increased from 0.35% in 2000 to 9,76% in 2008 (p<0,0001), and from then, decreased to 8.28% in 2011 (p<0.0001). There are also significant differences between races. In White’s BT increased 11.33% in 2008 which is 1.46 more times than in Black’s and 1.79 more than Hispanic, and then decreased to 9.52% in 2011 which is 1.61 more than in Black’s, and 1.64 more than Hispanic’s. Conclusions: The use of breast preservation RT has increased significantly in stages 0 to III from year 2000 to 2011. BT use increased until year 2008, when it begun to decrease until year 2009, stabilizing in 2010 and 2011 at around 8%. There are significant differences between races in the use of RT in general, and BT in particular, being Hispanic’s the ones which significantly received less breast preservation RT treatment. This finding raises important questions.
Cardiac dose evaluation in patients undergoing breast radiotherapy in the modern era.
Authors: Peters Christopher A. , Kaleda Andrew , Manfredo Anthony , Tapen Elizabeth , Koutcher Lawrence
Published: February 2017

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Background: Breast radiotherapy (RT) after conservative surgery improves overall survival and minimizes locoregional recurrence. The therapeutic ratio of adjuvant RT continues to improve with time. Cardiac toxicity from breast cancer treatment remains a concern, and can result from chemotherapy, biologic therapy, or RT in a dose-dependent fashion. Dose to avoidance structures can be minimized as technological improvements in radiotherapy evolve. We sought to investigate heart and coronary artery dose using modern RT techniques. Methods: We reviewed 164 consecutive non-metastatic breast cancer patients treated with adjuvant breast RT, from 3/2011 to 12/2013. 8 patients were excluded because they did not complete the prescribed dose. Patients were treated on 3 different machines, at 2 centers. Data was extracted using both the treatment planning system and electronic medical records. Univariate analysis was done using t-test and one way ANOVA for variables predicting higher mean heart dose (MHD). Multivariate analysis was performed using multiple linear regression. p values ≤0.05 were considered significant. Results: The median age of our cohort was 63 (range 33-85), and 90% had ≤ stage 2 disease. 53% had left sided RT, 45% right, and 2% had bilateral RT. 18% had breast/chest wall and nodal RT, with 2% dedicated IMN targeting. 22% of patients were treated prone. The median dose, including boost, was 60.4 Gy (range 42.4-66.4). 35% received cytotoxic chemotherapy and 10% received trastuzumab. Mean heart dose was 1.4Gy (SD 2.2), and mean LAD dose was 4.9Gy (SD 4.4). MHD were lower in the prone position compared to supine, but did not reach statistical significance p=0.3. Advanced AJCC stage grouping, left sided or bilateral treatment, breast/nodal target volume, and helical treatment were associated with significantly higher MHD on univariate analysis. On multivariate analysis, only breast/nodal volume and helical technique remained significant, both p<0.001. Conclusions: Modern techniques result in low heart and LAD doses in our series. Because adjuvant breast RT plays a critical role in the definitive management of breast cancer, these data are reassuring to patients, physicians, and payers.
The effects of hormonal replacement therapy (HRT) on mammographic breast density and abnormal mammograms prompting further investigation.
Authors: Barda Liran , Nevler Avinoam , Shabtai Esther L , Gutman Mordechai , Shabtai Moshe
Published: February 2017

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Background: Mammographic density has been associated with higher risk of breast cancer and lower sensitivity. HRT has been implicated with increased density and is also a risk factor. The relationship between HRT, breast density, and mammographic findings requiring investigation has not been fully investigated. We aimed at analyzing this correlation. Methods: 2,758 consecutive, single-center screening mammograms performed during 1 year were analyzed. Mammograms were supplemented by ultrasound. Density was measured by a semiquantitative, 5-grade scale, and grouped into low (1-3) (LDM) and high density (4-5) (HDM). Demographic and obstetric data, personal and family history of breast cancer, and the use of HRT were entered into database. These parameters were correlated with breast density and any abnormality detected. Univariate and multivariate analysis as well as multivariate logistic regression were performed on SAS 9.2. Results: Mean overall age was 48 (SD = 10.8, range 27-78), mean ages of LDM and HDM groups were 59 ± 10.5 and 50.9 ± 9.3 respectively (p = 0.001). Of 2,758 tests, 2,094 (76%) were LDM and 664 (24%) were HDM. 1,962 women (71%) were postmenopausal and 592 (30%) were on HRT. A difference in density between pre- and postmenopausal women was observed (p = 0.0001). HRT was not associated with higher rate of HDM (18%, n = 105/582) vs.15% n = 211/1370 (p = n.s) without HRT. Abnormality was more likely in postmenopausal HRT-less (52% n = 711/1370) vs. (30% n = 226/582) HRT (p = 0.0001) including solid lump (p = 0.0001), tissue irregularity (p = 0.016) and calcifications (p = 0.0005). Menopause was associated with 48% of any finding vs. 41.4% in pre-menopause women (p = 0.0017). 104 malignant lesions were found in 267 with mammographic findings prompting histological assessment. HRT was associated with lower incidence (28%) of malignancy compared to 50% without HRT. Conclusions: HRT was not associated with increased density nor with higher risk of malignancy; moreover, a lower rate of mammographic abnormality was noted. Albeit further studies are required, the results of this study do not support the notion that HRT increases the likelihood of malignancy or affects breast density.
Prognostic and predictable value of COX2 expression in Russian women with stage I breast cancer.
Authors: Kolyadina Irina Vladimirovna , Kuppen P. J. K. , Van De Velde Cornelis J. H. , Poddubnaya Irina Vladimirovna , Dekker-Ensink N.G. , Prinse B. , Frank G. , Karseladze A. , Komov D. , Engles C. , Ermilova V.
Published: February 2017

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Background: Some previous studies found worse prognosis among cyclooxygenase-2 (COX2)-expressing breast cancers; we study prognostic and predictiable value of COX2 expression in breast cancer stage I. Methods: our study included Russian women with breast cancer stage I (n=315) treated in RCRC, RMAPE (1985-2009). A Tissue Micro Array (TMA) with triplicate 1 mm tumor tissue punches taken from tumor blocks was constructed in LUMC; sections were immunohistochemically stained for ER, PR, HER2-status, Ki67 (by standard morphological criteria); COX2-expression were evaluated as positive (>median; 31/309 cases, 10%) or negative (≤median; 278/209 cases, 90%). Also the histological type, grade, age and adjuvant endocrine therapy were examined. We analyzed the clinic and morphological data of COX2-positive tumors, prognostic value for survival (relapses free- RFS, overall- OS and cancer specific- CSS) and predictable value for endocrine therapy. Results: COX2-positive tumor were associated with ductal histological type (p=0,018), PR-negative status (p=0,027) and high Ki67 (p<0,0001), but not correlated (p>0,05) with age, grade, ER, HER2 status or biological subtype. In women with ER-negative tumors (104 patients, 34,1%) COX2-expression did not associate with worse survival (p>0,05). In contrast to this, in patients with ER-positive tumors (201 women, 65,9%) COX2-expression strongly correlated with worse RFS in univariate (HR 2,829, 95% CI 1,366-5,860, p=0,005) and multivariate analyses (HR=2,972, 95% CI 1,190-7,423, p=0,02). The same value of COX2-expression in women with ER-positive tumors was found for CSS (univariate: HR 3,421, 95% CI 1,436-8,149, p=0,005; multivariate: HR 4,260, 95% CI 1,344-13,504, p=0,014), but not for OS (p>0,05). In women who did not receive adjuvant endocrine therapy (145 patients, 46%) COX2 expression did not have any prognostic value for RFS, OS and CSS (p>0,05) but in patients that used adjuvant endocrine therapy (170 women, 54%) COX2-expression strongly associated with worse cancer-specific survival (HR 5,614 95% CI 1,165-27,059, p=0,032), but not with RFS and OS (p>0,05). Conclusions: COX2 expression plays a role in hormonal pathways and sensitivity for endocrine therapy.