bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity and menopausal status as determinants of procarcinogenic breast inflammation.
Authors: Iyengar Neil M. , Morris Patrick Glyn , Zhou Xi Kathy , Gucalp Ayca , Giri Dilip D. , Harbus Michael , Falcone Domenick J , Vahdat Linda T. , Awad Mahmoud I. , Krasne Margaret D , Subbaramaiah Kotha , Morrow Monica , Hudis Clifford A. , Dannenberg Andrew
Published: February 2017

40

Background: Chronic inflammation predisposes to several malignancies. We previously demonstrated an obesity → inflammation → aromatase axis in breast tissue. As obesity is a risk factor for postmenopausal (PoM) but not premenopausal (PreM) breast cancer (BC), we examined whether menopause and body mass index (BMI) independently impact breast white adipose tissue (WAT) inflammation. Methods: WAT was prospectively collected from patients (pts) from 04/10 to 08/13. WAT inflammation, detected by CD68 immunohistochemistry, was defined by the presence of dead or dying adipocytes surrounded by an envelope of macrophages known as crown-like structures of the breast (CLS-B). WAT area was measured with NIH Image J. Adipocyte diameter was measured with Canvas 11 Software. Endpoints were 1) CLS-B (+/-) and 2) CLS-B/cm2. Clinicopathologic associations with CLS-B were analyzed by logistic regression and Fisher’s exact test. Results: WAT (237 mastectomies, 13 abdominal reconstructions) was obtained from 238 pts; median age 48 (range 22 to 90). CLS-B occurrence and number of CLS-B/cm2 were greater in overweight/obese (BMI ≥ 25) and PoM pts compared to lean (BMI < 25) and PreM pts (Table). In multivariable analyses, BMI and PoM state were independently associated with CLS-B presence (p <.01 and p = .04) and greater CLS-B/cm2(p < .01 and p = .01). PoM pts had larger mean adipocyte diameter (105.2 +/- 14.0 μ) than PreM pts (95.7 +/-15.6 μ; p < 0.01). In pts with bilateral breast WAT and abdominal WAT, concordant CLS status (+/-) was found in 49/63 (78%) and 10/13 (77%) pts, respectively. Conclusions: Breast WAT inflammation (both presence and severity), which we have previously linked to increased aromatase activity, is associated with both increased BMI and menopause. These findings can explain the increased risk of estrogen receptor–positive BC with obesity and PoM status and may also provide targets for rational therapies. [Table: see text]
Effect of human insulin on breast cancer risk in Taiwanese women with type 2 diabetes.
Authors: Tseng Chin-Hsiao
Published: February 2017

43

Background: Whether human insulin may induce breast cancer is rarely studied. Methods: The reimbursement databases of all Taiwanese patients with diabetes from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at January 1, 2004 and a total of 482,065 women with type 2 diabetes were followed up for breast-cancer incidence until the end of 2009. Incidences for ever-users, never-users, and subgroups of human insulin exposure (using tertile cutoffs of cumulative dose and cumulative duration of insulin) were calculated and the multivariable-adjusted hazard ratios were estimated by Cox regression. Results: There were 59,830 ever-users and 422,235 never-users, with respective numbers of incident breast cancer of 559 (0.93%) and 4,711 (1.12%), and respective incidence of 207.7 and 215.1 per 100,000 person-years. The overall adjusted hazard ratios (95% confidence intervals) did not show a significant association with insulin [1.098 (0.994-1.212)]. However, significant trends for the different categories of the dose-responsive parameters were observed. Patients in the third tertiles consistently showed a significantly higher risk of breast cancer compared to never-users: 1.339 (1.164-1.540) and 1.331 (1.158-1.531) for ≥ 39,000 units for cumulative dose of insulin, and ≥ 21.8 months for cumulative duration of insulin, respectively. Conclusions: This study discloses a significantly higher risk of breast cancer associated with the use of human insulin, demonstrating a significant dose-responsive relationship.
The impact of Angelina Jolie's (AJ) story on genetic referral and testing at an academic cancer centre.
Authors: Raphael Jacques , Verma Sunil , Hewitt Paul , Eisen Andrea
Published: February 2017

44

Background: In May 2013, AJ revealed to the media that she had undergone preventive double mastectomy. The actress had a family history of breast and ovarian cancer and tested positive for the BRCA1 gene mutation. Media coverage has been extensive, but it’s not clear what messages the public and professional medical staff took from this personal story that sometimes could be misleading. Methods: We conducted a retrospective review in our centre using data from the clinical database of the Familial Cancer Program in a tertiary care cancer centre. The impact of AJ’s story on genetic counseling referrals was assessed by comparing the number of referrals made 6 months before and after the story. In addition, the quality of referrals was reported by comparing the number of patients who qualified for genetic testing as defined by the Ontario Ministry of Health and Long Term Care and the ones who carried a BRCA1/2 mutation before and after the media release. Results: The number of women referred for genetic counseling increased by 85% after the release of AJ’s story (479 before versus 887 after). This translated to an increase of 99% in the number of women who qualified for a genetic testing (211 before versus 419 after). Among them, 120 and 254 women had a history of breast and ovarian cancer in their family, 16 and 37 women had a history of male breast cancer in their family, and 28 and 15 women were diagnosed with breast cancer at the age of 35 or less before and after AJ’s story respectively. Furthermore, the number of BRCA1/2 carriers identified increased by 107% (29 (14 BRCA1, 15 BRCA2) before and 60 (32 BRCA1, 28 BRCA2) after). Conclusions: This study clearly shows that the number of genetic referrals doubled after AJ’s story. Nevertheless, the quality of referral remained the same with nearly the same percentage of patients who qualified for genetic testing and who were identified as BRCA1/2 carriers. The challenge is to meet the increased demand for cancer genetic services including screening, counseling, testing, and preventive surgery. After AJ’s story the current model of genetic counseling may need to be revisited.
Comparison of the intermediate risk 21-gene recurrence score (RS) with the 70-gene signature (GS) as a continuous variable, Magee equations, and Adjuvant! Online (AOL).
Authors: Mai Hanh P. , Kliethermes Stephanie , McCroskey Zulfia , Ersahin Cagatay , Gaynor Ellen R. , Robinson Patricia A. , Albain Kathy S. , Lo Shelly S.
Published: February 2017

47

Background: Multigene assays and risk-prediction models are used to provide prognostic information in the management of patients with estrogen receptor positive (ER+) lymph node negative (LN-) breast cancer (BC). Some have predictive utility in determining the value of chemotherapy added to endocrine therapy. We previously reported a mix of high and low risk 70-GS within the intermediate risk 21-gene RS. The Magee equations provide an estimate of the 21-gene RS using standard pathological findings. AOL provides a 10-year risk of BC recurrence or death. The objective of this study is to evaluate correlations between the 70-GS as a nondichotomous continuous variable, the Magee equations, and AOL within patients (pts) with 21-gene intermediate RS. Methods: The 70-GS as a continuous variable (highest risk of -1 to lowest risk of +1) was obtained on all consecutive ER+LN- BC cases with an intermediate 21-gene RS at Loyola U Med Ctr from 1/2005 to 9/2012. AOL recurrence risk and the Magee equations were calculated from clinical-pathologic findings. Pearson pairwise correlations among all four recurrence measures were generated. Results: Results of the 70-GS as a continuous variable and the 21-gene RS were available in 89 cases. A higher risk 70-GS correlates with a higher 21-gene RS (r = -0.31; p = 0.003). A higher risk of recurrence as estimated by AOL is associated with a higher 21-gene RS (r = 0.22; p = 0.036), higher Magee equation 1 (r = 0.36; p = 0.001) and 2 (r = 0.32; p = 0.004), and a higher risk 70-GS (r = -0.40; p < 0.001). Magee equations 1 and 2 are statistically correlated to the 21-gene RS (r = 0.24; p = 0.028 and r = 0.23; p = 0.036 respectively), but not to the 70-GS (p = 0.064 and p = 0.057 respectively). Magee equation 3 is not statistically correlated with 70-GS, 21-gene RS or AOL. Conclusions: There is a continuum of highest to lowest risk 70-GS among LN- ER+ BC within intermediate risk RS. The prospective PROMIS study will assess if the 70-GS adds clinical utility regarding adjuvant therapy choice for these pts.
Incidence and survival of patients with T0N1 breast cancers.
Authors: Abe Shoko Emily , Carpenter Kendall W. , Han Yimei , Flippo Teresa , Sarantou Terry , Hill Joshua S. , White Richard L.
Published: February 2017

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Background: As imaging modalities have improved, breast cancers are increasingly detected at earlier stages. Patients rarely present with axillary disease but no mammographically evident breast tumor. Based on analysis of Surveillance, Epidemiology and End Results (SEER) data, we determined that there has been an increase in incidence of T1aN1 breast cancers. In response, we hypothesize that T0N1 breast cancer incidence has decreased with increased MRI use. Moreover, SEER analysis showed that T1aN1 patients have worse survival than T1bN1 patients. We thus hypothesize that T0N1 patients have worse survival than T1N1 patients. Methods: We identified 36,093 female patients diagnosed with T0-1 N1 invasive breast cancer from the SEER database. We compared patient and tumor characteristics: age, race, histology, hormone receptor status, and diagnosis year group (1990-1994, 1995-1999, 2000-2005, 2006-2010) – by TN category (T0N1/T1aN1/T1bN1/T1cN1) using chi-square test and ANOVA. Kaplan-Meier method was used to estimate disease specific survival (DSS) for each TN category and diagnosis year group separately. Adjusted hazard ratios were estimated using Cox proportional hazards models. Results: Stage distribution was: T0N1=129, T1aN1=1294, T1bN1=6731, and T1cN1=27942 patients. Median ages were 59.6, 56.3, 59.1, and 58.1, respectively. Time trend analysis of T0N1 cancers showed an increase in incidence from 1990 to 1999 and stability after 2000. Five-year DSS was significantly worse for patients with T0N1 tumors than T1aN1 tumors (84.5% versus 94.1%, HR 0.513, p < 0.0001). T0N1 tumors were more likely to be ER negative than T1b-cN1 tumors (23% versus 16%, p < 0.0001). T0N1 tumors were also more likely to be ER negative than T1aN1 tumors, but did not reach statistical significance (23% vs. 20%, p = 0.09). The proportion of lobular cancers was significantly higher in T0N1 than T1aN1 or T1b-cN1 patients (18% versus 8%, p < 0.0001). Conclusions: Our analysis suggests that T0N1 tumors may differ biologically from T1N1 tumors. Although the incidence of T0N1 tumors did not decrease, it remained stable after 2000 when the use of MRI for occult breast cancers became widely accepted. Our second hypothesis that survival is worse in patients with T0N1 tumors was confirmed by our analysis.
Factors associated with increasing rates of contralateral prophylactic mastectomy.
Authors: Yakoub Danny , Avisar Eli , Koru-Sengul Tulay , Miao Feng , Tannenbaum Stacey L. , Byrne Margaret M , Moffat Frederick L. , Livingstone Alan S , Franceschi Dido
Published: February 2017

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Background: Contralateral prophylactic mastectomy (CPM) is an option increasingly used by women who wish to reduce their risk of breast cancer or its local recurrence. There is limited data on demographic differences among patients who choose to undergo this procedure. Methods: The population-based Florida cancer registry, Florida’s Agency for Health Care Administration (AHCA) data, and U.S. census data were linked and queried for patients diagnosed with invasive breast cancer from 1996 to 2009. The main outcome variable was the rate of CPM in those with a single unilateral cancer diagnosis. Primary predictors were race, ethnicity, socioeconomic status (SES), marital status, and insurance status. Results: The rates of CPM rose from 2% in 1996 to 4.8% in 2006 up to 8% in 2009. The population studied was 91.1% white and 7.5% black; 89.1% non-Hispanic and 10.9% Hispanic. Out of 21,608 included patients, 837 (3.9%) underwent CPM. Significantly more white than black (3.9 versus 2.8%; p < 0.001) and more Hispanic than non-Hispanic (4.5 versus 3.8%; p = 0.0909) underwent CPM. Those in the highest SES category had higher rates of CPM compared to the lowest SES category (5.3 versus 2.9%; p < 0.001). In multivariate analyses, Blacks and uninsured patients had significantly less CPM compared to whites and private patients (OR = 0.59, 95% CI 0.42- 0.83, p = 0.002) and (OR = 0.60, 95% CI 0.36- 0.98, p = 0.043), respectively. Conclusions: CPM rates are significantly increasing; these rates were significantly different among patients of different race, socioeconomic class, and insurance coverage. This observation is not accounted for by population distribution, incidence or disease stage. More in-depth study of the causes of this increase and the disparities in healthcare delivery is critically needed.
Racial/ethnic disparities in clinicopathologic features and treatment modalities of triple-negative breast cancer in black premenopausal women.
Authors: Hamid Muhammad S , Shameem Raji , Pudusseri Anita , Graham Robert , Shani Dana , Sullivan Kevin M.
Published: February 2017

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Background: Triple-negative breast cancer (TNBC) is a distinct breast cancer subtype associated with poor outcomes. Previous literature has reported an increased prevalence of TNBC in premenopausal black women. However, clinicopathologic features and treatment disparities of TNBC require further investigation. Methods: We used the Surveillance Epidemiology and End Results (SEER) database to collect data for premenopausal, estrogen receptor–negative, progesterone receptor–negative, and HER2 receptor–negative invasive breast-cancer cases diagnosed in 2010. Blacks were compared to the referent non-Hispanic white (NHW) cohort. Variables explored include: age at diagnosis, summary stage, tumor size, presence of metastasis at diagnosis, birth country, marital status, radiation, surgery (total and partial mastectomy), and radiation/surgery sequence. The Kruskall-Wallis test and the Z-test were used to investigate for any racial/ethnic disparities that may exist. Results: Compared to NHW, black patients had more regional disease (42.3% vs. 36.1%, p < 0.05) and distant metastasis (7.37% vs. 4.67%, p < 0.05) at the time of diagnosis, They were more likely to be single (44.0% vs. 17.1%, p < 0.05), born in the United States (39.4% vs. 32.5%, p < 0.05), have fewer cases in the “40-49 years” age range (68.6% vs. 73.0%, p < 0.05), and present with tumor size > 20 mm (26.1% vs. 36.6%, p < 0.05) compared to NHW. While black women received surgical intervention (11.5% vs. 6.8%, p < 0.05) more commonly, adjuvant radiation (41.0% vs. 33.3%, p < 0.05) was utilized less after segmental mastectomy compared to NHW. Conclusions: Poor prognostic tumor characteristics were significantly more likely to be present in black premenopausal women with TNBC compared with NHW patients. Black women were more likely to receive surgical intervention, however, adjuvant radiation was administered significantly less. Further research is necessary to clarify if these disparities have an impact on survival outcomes.
Nomogram for predicting the risk of locoregional recurrence in patients treated with accelerated partial-breast irradiation.
Authors: Wobb Jessica , Chen Peter Y. , Shah Chirag , Moran Meena S. , Shaitelman Simona Flora , Vicini Frank A. , Mbah Alfred K. , Lyden Maureen , Beitsch Peter D.
Published: February 2017

59

Background: There are limited tools to guide clinicians regarding the risk of locoregional recurrence (LRR) in patients wishing to pursue APBI. The purpose of this study was to develop a nomogram taking into account clinicopathologic features to predict LRR in patients treated with APBI for early stage breast cancer. Methods: A total of 2,000 breasts (1,990 women) were treated with APBI at William Beaumont Hospital (N=551) or on the ASBrS MammoSite Registry Trial (N=1,449). Techniques included multiplanar interstitial catheters (N=98), balloon-based brachytherapy (N=1,689), and 3D conformal radiotherapy (N=213). Clinicopathologic variables were gathered prospectively. A nomogram was formulated utilizing the Cox Proportional Hazards Regression model to predict for LRR. This was validated by generating a bias-corrected index and cross-validated with a C-index. Results: Median follow-up was 5.5 years (0.9 to 18.3). Of the 2,000 cases, 435 were excluded due to missing data. Univariate analysis found that age <50, pre/perimenopausal status, close/positive margins, ER negativity, and high grade were associated with a higher frequency of LRR. These five independent covariates were used to create adjusted estimates, weighting each on a scale of 0 to 100. The total score is identified on a points scale to obtain the probability of an LRR over the study period. The model demonstrated good concordance for predicting LRR with a C-index of 0.641. Conclusions: The formulation of a practical, easy-to-use nomogram for calculating the risk of LRR in patients undergoing APBI will help guide the appropriate selection of patients for off-protocol utilization of APBI.
Locoregional recurrence (LRR) after neoadjuvant chemotherapy (NAC): Pooled-analysis results from the Collaborative Trials in Neoadjuvant Breast Cancer (CTNeoBC).
Authors: Mamounas Eleftherios P. , Cortazar Patricia , Zhang Lijun , Von Minckwitz Gunter , Mehta Keyur , Cameron David A. , Bonnefoi Herve R. , Gianni Luca , Valagussa Pinuccia , Wolmark Norman , Loibl Sibylle , Bogaerts Jan , Swain Sandra M. , Sridhara Rajeshwari , Costantino Joseph P. , Rastogi Priya , Geyer Charles E. , Eidtmann Holger , Gerber Bernd , Untch Michael
Published: February 2017

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Background: There is limited information on LRR rates in pts treated with NAC. Methods: 12 large NAC BC trials (11,955 pts) with pCR information and long-term F/U for LRR, EFS and OS were included. Primary aims were to assess LRR rates by pCR, tumor subtype, surgery type and other clinico-pathologic factors. Main definition of pCR was ypT0/is ypN0. Results: Median F/U: 5.4 years. Median age: 49, T2 tumors: 61%, Inflammatory BC: 4%; Clinically(+) nodes: 47%. Overall LRR: 6.8% (95% CI: 6.3, 7.2). LRR was 5.5% with pCR (ypT0/isypN0) vs. 7.1% without. After lumpectomy, LRR rates were similar with pCR (6.0%) vs. without (6.3%). After mastectomy, LRR rates were lower with pCR (3.8%) vs. without (8.1%), irrespective of XRT use. In HR(+)/HER2(-) BC, LRR rates were low with pCR (1.9%) or without (3.3%) with similarly low LRR rates in grade 1/2 tumors (pCR: 2%, no-pCR: 2.6%). In HR(+)/HER2(-)/grade 3 BC LRR rates were lower with pCR (1%) vs. without (5.3%). In HER2(+) BC LRR rates were similar with pCR (5.1%) or without (7.3%), mainly seen in HER2(+)/HR(+) BC (5.7% vs. 5.5%). In contrast, in HER2(+)/HR(-) BC LRR rates were lower with pCR (4.9%) vs. without (9.8%). Also, in HR(-) /HER2(-) BC LRR rates were lower with pCR (4.9%) vs. without (8.6%). LRR varied with path nodal status and TNM stage at surgery: node(-): 5.6% vs. node(+) 8.9%; stage 0: 5.3%; stage 1: 5.2%; stage 2: 7.3%; stage 3: 10.1%. Conclusions: LRR rates after NAC are low and vary by pCR status, tumor subtype, type of surgery, stage and path nodal status. This information may have clinical implications on selecting appropriate candidates for XRT. [Table: see text]
Late axillary recurrence after negative SLNB.
Authors: Matsen Cindy Brown , Villegas Kristine , Eaton Anne , Stempel Michelle , Manning Aidan , Morrow Monica , Heerdt Alexandra S.
Published: February 2017

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Background: SLNB is the standard axillary evaluation method for clinically node-negative patients with invasive breast cancer. While axillary recurrence (AR) in the early years after negative SLNB is <2%, studies with longer (>8 yrs) follow-up on large patient numbers are lacking. With concern that current multimodality therapy may delay time to AR, we reviewed long-term SLNB patient outcomes. Methods: We identified patients with invasive cancer from a prospective, single-institution database who had a negative SLNB without additional axillary surgery from 1/97-12/00. Cancer, demographic, and treatment data were obtained for all patients. Primary outcome was AR. Overall survival (OS) and distant disease-free survival (DDFS) after AR were secondary endpoints. Results: 1529 eligible patients were identified. See table for patient and tumor characteristics. At 10.8 yrs (0-16) median follow-up, overall incidence of AR as a first event was low, n= 13. Median OS after AR was 4.6 yrs and median DDFS after AR was 3.8 yrs. The cumulative incidence of AR was 1.0% (CI 0.5-1.6) overall; cumulative incidence of 0.6% (CI 0.2-0.9) in the first 5 years, 0.4% years 5-10. Late AR (>5 yrs) occurred in 5 patients: 4 ER+, 1 HER2+. In comparison, in a group of contemporaneous SLNB-positive patients undergoing axillary dissection (n=902), overall cumulative incidence of AR was 0.8% (CI 0.2-1.5) at over 10 yrs follow-up. On univariate analysis of AR in SLNB-negative patients, high nuclear grade was the only significant predictor of AR (p=0.01). Conclusions: Late AR was an infrequent event after negative SLNB alone emphasizing its long-term safety as a staging procedure. AR after SLNB, like AR after ALND, portends a poor prognosis.[Table: see text]
Trends in breast cancer treatment in United States from 2000 to 2011: Consequences of 2004 National Comprehensive Cancer Network (NCCN) guidelines change.
Authors: Arrojo Elisabeth E. , Martinez Alvaro , Vicini Frank A.
Published: February 2017

69

Background: In 2004, the NCCN, changed the guidelines for the treatment of stage 1, HR+, > 70 years(y) breast cancer patients, based mainly on the CALGB/RTOG trial, which showed that in these patients, the addition of radiotherapy (RT) to surgery and tamoxifen did not improve overall survival, but significantly decreased local relapse at 5 y. Methods: Retrospective analysis about trends in breast cancer treatment in USA from years 2000 to 2011, searching the National Cancer Data Base, reviewing 458.386 cases of breast cancer stage I, HR+, with special focus in patients >70y. Chi square test was used. Results: Between years 2000-2011, in the group reviewed, mastectomy (MT) increased in women <40y (+25%) and between 40-69y (+13%), while RT decreased in both groups (-20%, -3%). In women >70y, MT decreased (-27%) progressively along these years, but radiotherapy increased until year 2003 (+3%), and begun to decrease in 2004 (-4%), with a final difference between 2003 and 2011 of -9%. In patients >70 y, chemotherapy (CH) treatments, increased progressively (+3%) from year 2000 to 2011 (p<0.001). Conclusions: Changes in NCCN breast cancer guidelines made in 2004, seem to have changed trends of breast cancer treatment in USA in patients > 70y, stage I, HR+. Since then, less aggressive “local” treatments (-4% for MT and -9% for RT) are been performed. Despite this trend for less local therapy chemotherapy utilization has increased even though the risk of systemic disease is very low. The main risk for these patients is local failure with the associated physical, psychological and family impact as well as cost of re-staging. Local RT has demonstrated a significant reduction of this risk. Today's life expectancy for a 70 y/o woman is >10y consequently local relapses and its consequences are expected. New RT techniques, such as partial breast irradiation delivered in few days are convenient and associated with very low toxicity and no mortality. Perhaps a re-look of the NCCN guidelines might be in order. [Table: see text]
A retrospective comparison of contrast enhanced spectral mammography (CESM) to breast MRI in breast cancer detection: An initial study for sensitivity analysis.
Authors: Li Luna , Brill Kristin , Germaine Pauline , Tinney Elizabeth , Hendershott Karen , Liao Lydia
Published: February 2017

7

Background: CESM is a new study using contrast and dual energy digital mammographic technology to detect contrast enhanced cancer that may be invisible on conventional mammogram. Limited studies have shown that adding CESM to diagnostic workup adjunct with mammogram and breast ultrasound does increase sensitivity for breast cancer detection. More studies are needed to compare the sensitivity of CESM to BMRI to further define the role of CESM in breast cancer diagnosis. Methods: This study involved 50 malignant breasts in 48 women retrospectively chosen from of 960 patients in our institution during the period of October 2012 to March 2014. Both CESM and BMRI were done for each patient within 30 days. The cancer diagnoses were confirmed by tissue diagnoses. The size of lesions was classified into three categories based on standard of breast cancer stages: 1 (0.2cm - < = 2 cm), 2 (2 cm < lesion < = 5 cm), 3 (> 5 cm). The enhancement intensity of both lesions and background has been quantified based on a scale of 0-3. Statistical significance was analyzed using T test for mean size of index cancer and mean score of enhancement intensity of background and lesions on CESM and BMRI. Sensitivity and positive predictive value (PPV) were calculated for both CESM and BMRI. Morphology consistence was calculated on both studies. Results: Both CESM and BMRI have sensitivity of 100% for breast cancer detection. CESM has a PPV of 98% versus 93% for BMRI. No statistical significance was identified on mean size of index cancer. The enhancement intensity of background and lesions is significantly higher on CESM than on BMRI (p < 0.01). The smallest cancer can be detected by both CESM and BMRI is less than 0.5 cm. Morphology consistence was 46/50 (92%). Conclusions: Our study indicates that CESM and BMRI have comparable high sensitivity on breast cancer detection. CESM has a higher PPV than BMRI that may indicate a better specificity (no significant difference due to the small sample size). Significantly less background enhancement intensity on CESM than on BMRI reflect an increased specificity. More studies need to be conducted for further evaluation.
Do women younger than 40 treated in the hormone-therapy era benefit from a radiotherapy boost as a part of adjuvant breast radiotherapy?
Authors: Tyldesley Scott , Chan Elisa K. , Speers Caroline , Nichol Alan
Published: February 2017

72

Background: The EORTC 22881 trial showed a 10% reduction in local relapse with a radiotherapy boost (RTB) after breast conserving therapy (BCT) among women ≤40 years old. However no premenopausal patients received hormone therapy (HT) in this study. A policy change in December 1998 recommended the use of HT after chemotherapy for premenopausal ER positive women. A second policy change in December 2001 recommended an RTB after BCT for women ≤40 years old. The purpose of our study was to describe: 1)how the use of HT and RTB after BCT changed after practice guidelines were implemented in a population-based cancer care program; and 2) how local relapse rates (LRR) changed after these policy changes. Methods: A provincial database was used to analyse all women ≤ 40 years old referred for consideration of radiotherapy with margin negative stage 1 and 2 (≤3 nodes positive) breast cancer, treated with lumpectomy and whole breast radiotherapy. Cases were grouped into three eras according to policy transition with 3 month gaps: 1) Jan 1996-Sep 1998, 2) Jan 1999-Sep 2001, 3) Jan 2002 to Sep 2004. Changes in the use of HT and RTB over these eras were assessed. Eight year LR-free survival was calculated using the Kaplan-Meier method and the three eras compared using log rank tests. Multivariable analysis (MVA) was performed including era, size of tumour, nodal status (0 vs 1-3), grade, lymphovascular space invasion (LVI), and use of chemotherapy. Results: There were 130 eligible patients from Era 1, 145 patients from Era 2, and 140 patients from Era 3. ER status did not differ across eras. HT was used for ER positive patients in 13% of Era 1, 68% of Era 2, and 83% of Era 3 cases (p<0.001). RTB was used in 40% of Era 1, 28% of Era 2, and 77% of Era 3 patients (p<0.001). LRR at 8 years were 87.3% Era 1, 94.8 % Era 2, and 94.5% Era 3 (p=0.03). Era (used as surrogate for transitions in the use of HT and RTB) remained significant on MVA (0=0.008). Conclusions: Patterns of use of HT and RTB changed after policy changes. The benefit of adding a boost in women ≤40 years old shown by the EORTC was not observed after the introduction of routine HT at a population level.
Effect of tumor subtype on overall survival in brain metastatic breast cancer patients treated with cranial irradiation.
Authors: Villgran Vipin Das , Mathew Aju , Rosenzweig Margaret Quinn , Abberbock Shira , Naik Rohan Dilipbhai , Jacob Mini , Jankowitz Rachel Catherine , Puhalla Shannon , Lembersky Barry C. , Brufsky Adam
Published: February 2017

74

Background: Brain metastatic breast cancer (BMBC) is often treated with whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) or both. Breast cancer tumor subtypes defined by hormone receptor (HR) and HER2 status have an important prognostic role in metastatic disease. It is unclear if tumor subtypes have a prognostic role in patients receiving WBRT or SRS. We aimed to investigate the association between breast cancer subtype and overall survival (OS) among BMBC patients treated with WBRT and SRS. Methods: In a single-institution cohort study, BMBC patients treated with WBRT/SRS during 1997-2013 were identified. Clinico-pathological characteristics and survival information were prospectively collected. Tumor subtype category were defined as HR+/HER2-, HER2+/HR+, HER2+/HR- and triple negative (TN). WBRT category patients received that modality and SRS category patients, only SRS for treatment of brain metastases. OS is defined as time from diagnosis of brain metastasis to death or last follow-up. We conducted univariate analyses using the Kaplan-Meier method and log-rank tests and multivariate analysis using Cox proportional hazards models. Results: Among 193 BMBC patients who received WBRT or SRS, 62 received just SRS, and among them, 45% was HR+/HER2-. The distribution of subtypes was similar in WBRT patients. The median OS in SRS group was 15 months (95% CI 11-18) compared to WBRT with 10 months (95% CI 7-14) (p=0.03). Among patients receiving WBRT, median OS in HER2+/HR- tumor was 30 months (95% CI 13-37), HER2+/HR+ tumor - 14 months (95% CI 5-24), HER2-/HR+ tumor - 8 months (95% CI 4-11) and TN - 5 months (95% CI 3-9) (P=0.0003). There was no significant difference in OS between the breast cancer subtypes among SRS patients: median OS among patients with HER2+/HR- tumor was 11 months (95% CI 5–27), HER2+/HR+ tumor - 25 months (95% CI 7-32), HER2-/HR+ tumor - 18 months (95% CI 14-32), and TN - 12 months (95% CI 3-24) (p=0.07). Conclusions: Among patients with BMBC,tumor subtype is a prognostic factor for survival in those who received WBRT. Tumor subtype provided no prognostic information for those who were treated with only SRS.
Dosimetric predictors of toxicity and cosmesis in women treated with hypofractionated whole-breast irradiation.
Authors: Dilworth Joshua T. , Hymas Richard Val , Jawad Maha Saada , Mangona Victor S. , Zamdborg Leonid , Wobb Jessica , Pietron Arielle , Wallace Michelle , Chen Peter Y. , Grills Inga S. , Brabbins Donald S.
Published: February 2017

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Background: Large breast volume (BV) and distance of separation (DoS) have historically served as exclusionary criteria for hypofractionated whole breast irradiation (H-WBI). We investigate dosimetric parameters impacting toxicity and cosmesis. Methods: 299 consecutive patients with T0-2,N0-1,M0 breast cancer were treated with H-WBI at a single institution from 2007-2013. 4,256 cGy were delivered in 16 fractions via tangent photon beams utilizing inverse planning, with objectives to limit the V105 to 15%, the V110 to 2%, and the V115% to <0.1%. 227 patients with available treatment planning information and at least 6 months of follow-up (FU) were analyzed. Dosimetric parameters were correlated with acute (≤6 months post-treatment) and chronic toxicity and overall cosmesis. Proportions of toxicity grade and cosmesis score were compared with chi-square or Fisher exact tests. Results: With a median FU of 2.7 years (range 0.4-6.6 years), there were no local or regional recurrences, 1 distant failure, and one in-field angiosarcoma. Rates of any acute and chronic grade 1/2/3 toxicity were 47%/32%/9% and 53%/22%/7%. Cosmesis (beyond 6 months) was reported as excellent, good, and fair in 45%, 55%, and <1% of patients. The V105 was the best predictor for cosmesis and chronic toxicity, with a V105≤10% being associated with better cosmesis (excellent vs fair/poor) and lower toxicity (grade 0 vs grade 1 vs grade 2/3) compared to a V105>10% (p=0.09 and 0.03, respectively). The mean DoS was 22 cm, with 22% and 3% of patients having a DoS greater than 25 cm and 28 cm. The mean BV was 1523 cc, with 19% and 5% having a BV greater than 2000 cc and 2500 cc. Neither a larger DoS nor a larger BV correlated with an inability to achieve a V105≤10% (p= 0.37 and p=0.13, respectively). Neither DoS nor BV predicted for worse acute toxicity, chronic toxicity, or cosmesis. Conclusions: Minimizing the V110 and V115 and limiting the V105 to ≤10% are useful dosimetric objectives to achieve excellent or good cosmesis following H-WBI. Acceptable toxicity and excellent cosmesis are achievable in women with large DoS or BV, provided techniques to maximize dose homogeneity are employed.
Combined experience at three breast centers with routine use of an intraoperative margin assessment device including comparison to historical re-excision rates.
Authors: Sebastian Mary L. , Police Alice Marie , Akbari Stephanie , Anglin Beth
Published: February 2017

79

Background: Historically there has been a high rate of surgical interventions to obtain clear margins for breast cancer patients undergoing breast conserving local therapy. This study is the first compellation of data among three breast centers to assess the impact of an intraoperative margin assessment tool (MarginProbe) on re-excision rates. This device has been approved for clinical use in the United States since 2013. We present groups of consecutive patients in each of these breast centers – before and after the implementation of routine intraoperative use of the margin assessment device during lumpectomy procedures. Methods: Lesions were localized by standard methods. The intraoperative margin assessment device was used on all circumferential margins of the main specimen, but not on any additional shavings. A positive reading by the device led to an additional shaving of the corresponding cavity location. Specimens were also imaged intra-operatively by X-ray, and additional shavings were taken if needed based on clinical assessment. We established the historical re-excision rates of each surgeon on a consecutive set of patients in a corresponding period just before we began using the device. Results: In total, 165 patients were treated in three institutions up until April 2014. Sixteen patients (9.7%, 16/165) required re-excision. Historical re-excision rates corresponding to periods of use before the intraoperative margin assessment device was put into use were 25.8% (48/186). The re-excision rate was reduced by 62% (P<0.0001). Six re-excisions were due to a positive shaving which was not measured by the device. Conclusions: Use of an intraoperative margin assessment device contributes to achieving clear margins and reducing re-excision procedures. As in some cases positive margins were found on shavings, future studies of interest may include an analysis of the effect of using the device on the shavings intra-operatively.
Discrepancies in three commercial prognostic breast cancer assays used in adjuvant chemotherapy decisions.
Authors: Bayewitz Ashrei Y , Schneider Jeffrey Gary , Ogden Lorna , Turi George
Published: February 2017

84

Background: OT (Oncotype DX), MS (Mammostrat) and MP (Mammaprint) are three prognostic measures of breast cancer recurrence risk. All three were retrospectively validated in large patient cohorts and are now used when deciding on risk-reducing adjuvant chemotherapy. Our objective was to directly compare these three assays and their potential for differential effects on adjuvant chemotherapy decision making. Methods: We have previously reported that OT reduces adjuvant chemotherapy utilization, whereas MS did not exhibit this same net tendency in identical patients. In this study, we performed MP assays in 31 ER+ N0 breast cancer patients for which we already had OT and MS results. Decision analysis was applied to determine changes in management that would be most likely depending on which assay was used to guide decision making. Results: Our decision analysis demonstrated that in a substantial proportion of breast cancer patients, each of the three assays led to changes in adjuvant treatment decisions compared with what would have been chosen based upon conventional criteria alone. OT changed the decision in 55% of patients, and MS and MP would have changed those decisions in 45% and 65% of patients, respectively. In two-by-two paired analyses, treatment decisions would have differed in 61% of cases for OT versus MS; 29% for OT versus MP and 38% for MS versus MP. OT had the greatest tendency to eliminate adjuvant chemotherapy use (in 55% of patients versus MS and in 22% of patients versus MP), whereas MS had the greatest tendency to increase chemotherapy use (in 55% of patients versus OT and 35% versus MP). Conclusions: In this study of 31ER+ N0 breast cancer patients, three commercially available prognostic assays (OT, MS and MP) often yielded discordant risk category results. Our decision analysis suggests that these discordant results may frequently lead to different chemotherapy choices based upon which assay had been selected to guide decision making.
Mean radiation dose to the heart in patients with left breast cancer with and without breath-hold technique.
Authors: Jacobson Geraldine M. , Watson Christopher Nicholas , Zhang Jianjun , Wen Sijin , Bunda-Randall Nicole Helen
Published: February 2017

85

Background: Mean heart dose (MHD) from breast irradiation has been correlated with late risk of ischemic heart disease. We previously reported using 3-D conformal radiation with field-in-field forward planning and heart blocking; MHD is substantially lower than described for patients treated before 2001. To further reduce MHD, we treated eligible patients with left breast cancer with breath hold technique. We compared the MHD with and without breath hold technique. Methods: We reviewed 45 radiation treatment plans of patients treated to the left breast from 5/2013-5/2014. All patients were evaluated for breath hold technique. Criteria were ability to hold the breath for 20 seconds and a stable chest position. 18 patients were treated with breath hold (BH), 27 patients with non-breath hold (NBH). All treatment plans were CT-based, 3-D conformal with field-in- field forward planning and heart blocking. Two treatment regimens were used: hypofractionation (HF) (16 x 2.66 Gy, no boost) or standard fractionation (SF) (46.8-50.4 Gy, +/- 10 Gy boost). Fisher's exact test and t-test were used to assess the data between MHD with breath hold (BH) and without (NBH). Results: Average MHD was 1.03 Gy (0.59-1.7) in BH patients, in comparison to 1.57 Gy (0.89-2.50) in NBH patients p<0.0001). MHD was associated with total breast dose (p=0.01) and BH patients were younger, average age 55.78 years (21.41-48.37) vs NBH, average 62.78 years (38-82). There was no association between breath hold and BMI. BH BMI average 34.12 (21.41-48.37), NBH average BMI 32.6 (20.58-44.71) p=0.46. Conclusions: Patients treated with radiation to the left breast with breath hold technique had significantly lower MHD than those treated with non-breath hold. (p=0.0001) Breath hold eligible patients tended to be younger; there was no relation between breath hold eligibility and BMI.
Outcomes of patients with triple-negative breast cancer treated with radiation therapy.
Authors: Yadav Siddhartha , Jawad Maha Saada , Wobb Jessica , Wilkinson J. Ben , Yadav Dhiraj , Wallace Michelle , Barnes Michael A , Grills Inga S.
Published: February 2017

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Background: This study compares outcomes between different types of loco-regional treatment modalities used in patients with triple negative breast cancers. Methods: 299 patients with triple negative breast cancer diagnosed between April 2004 and August 2011 at a single institution and who were treated with radiation therapy were included in an IRB-approved retrospective review. Electronic charts were reviewed for demographic and pathologic data as well as outcome data including locoregional and distant recurrence. The median follow up period was 3 years. 200 (70%) patients underwent lumpectomy with whole breast irradiation (WBI). 68 (22.7%) patients received mastectomy and radiation while 31(10.4%) patients were treated with lumpectomy with accelerated partial breast irradiation (APBI). Results: Forty-nine patients (16.4%) experienced recurrence (10 local; 6 contralateral; 3 regional; 36 distant). There was a significant (p<0.0001) difference in the proportion of patients that experienced a recurrence in each treatment group: 34% (n=23) in mastectomy with radiation group; 12% (n=23) in lumpectomy with WBI group; 10% (n=3) in lumpectomy with APBI group. On univariate analysis, tumor size, tumor stage, nodal stage, overall stage, total number of positive nodes, total number of nodes removed, and whether or not the patients had an axillary lymph node dissection were significantly associated with recurrence (p<0.05). When these predictor variables, including treatment type, were examined using a stepwise cox proportional hazards regression model for recurrence, the only variables that remained significant were tumor stage (p= 0.0003) and the number of positive nodes (p= 0.0008). Survival curves were significantly different (p = 0.016) between the lumpectomy with WBI group and the mastectomy with radiation group. Over all follow-up times, the probability of survival was smallest for the mastectomy with radiation group. Conclusions: The recurrence pattern for triple negative breast cancers treated with radiation therapy was primarily distant for all treatment modalities. In our patient population, tumor stage and number of positive lymph nodes predicted for recurrence while radiotherapy technique did not.
Ideal breast volume resection during wide local excision: Is it ∏ in the sky?
Authors: Hillick Dearbhla , Shanley Eoghan , Mohd Noor Aslam , Johnston Alison , Sugrue Michael
Published: February 2017

91

Background: Despite advances in imaging and pre-operative work-up, there is significant variability in breast volume excision, margin positivity and re-excision rates in wide local excision (WLE) surgery. Suggested ideal resection volumes and benchmarks for maximal % breast volume excision have been suggested (Krekel N, Zonderhuis B, Muller S et al (2011). Excessive Resections in Breast Conserving Surgery A Retrospective Multicentre Study. The Breast Journal 17 (6): 602-609). This study assessed whether there was much difference between actual and expected breast specimen volumes, allowing for tumour size variation. Methods: A retrospective review was undertaken of symptomatic patients undergoing WLE in a single breast surgeon’s practice between May 2011 and May 2013 at a designated breast cancer centre. Patients with DCIS were not included. Modified Krekel optimal resection volumes (ORV) [4/3 π (r+1.0cm)3] were estimated to include 1.0cm, 1.5cm and 2.0cm macroscopic margins. Breast volume was calculated using Katariya and Kalbhen mammographic formulae. Excess resection was defined as the difference between total specimen and optimal specimen volume. Results: 50 consecutive patients, mean age 63 years (range 38-88), mean BMI 28.1 ±4.8, mean tumour size 24.0 ±11.5cm3 were studied. Of the 50 patients 44/50 (88%) had a palpable tumour. 52% had T2 tumours, 68% had associated DCIS and 32% were node positive. Mean specimen weight was 78.6g ±1. Mean optimal and actual breast resection volumes were 42.6 ±37.3 cm3and 160 ±102.4 cm3; 6/50 had positive margins leading to re-excision in 4. The mean breast and specimen resection volumes were 815 ±327.4cm3 and 225 ±153.8 cm3 resulting in a mean percentage breast volume excision of 19.3 ±99%. Potential excess resection in 48/50 patients with a mean excess resection volume of 182.7 ±145 cm3. Conclusions: This study identified the opportunity to improve consistency in the volume of breast resected. Determining ideal volume resection should be part of patient surgical oncological planning.
Diagnostic delay in young women with breast cancer: A population-based analysis.
Authors: Quan May Lynn , Austin Janice , Lam Nadine , Quinn Rob
Published: February 2017

92

Background: Breast cancer in young women is aggressive. Delays in diagnosis and treatment may contribute to the worse outcomes observed in the treatment of breast cancer in young women. The purpose of this study is to determine if there was diagnostic delay for women ≤ 35 with breast cancer in Alberta. Methods: We conducted a population based analysis of all women ≤ 35 treated for breast cancer between 2007 and 2010. Patient demographics, diagnostic modality, and time to treatment (surgery and radiation) were abstracted. “Diagnostic” and “treatment” delay were defined as ≥ 90 days from first imaging to pathologic diagnosis and pathologic diagnosis to surgery. Results: One hundred and one patient charts were identified in the Alberta Cancer Registry and reviewed. Mean age at diagnosis was 31.6 (± 3.3) years. Initial imaging modality was mammogram and ultrasound in 49.5% and 46.5% of women. The median time from imaging to pathologic diagnosis was 6 days (range 0-502). Of these, 11 (10.1%) women experienced diagnostic delay, with a median delay of 131 days (range 95-502). The stage at diagnosis was not significantly different for women with and without diagnostic delay (p = 0.47). For women with diagnostic delay, the initial imaging findings were most often reported as likely benign or recommended only follow up imaging. Mean time from diagnosis to surgery was 25 (± 14) days. Of patients undergoing surgery, 25 (24.8%) had breast conserving surgery. Radiation therapy occurred at a median of 48 (range 25-204) days post operatively or post chemotherapy. Conclusions: Ten percent of women ≤ 35 with breast cancer experienced a diagnostic delay. Diagnostic delay most often occurred due to initial imaging reports of benign or negative findings. Further studies are required to determine the impact of diagnostic delay on patient outcomes.