bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost comparison of radiation treatment options after lumpectomy for breast cancer: Intraoperative radiotherapy versus alternatives.
Authors: Holmes Dennis R. , Pulicharamveettil Juvairiya , Sutter Gary Lee , Rivera Ronald J.
Published: February 2017

187

Background: Increasing constraints on health care resources call for implementation of breast cancer treatment strategies that preserve treatment efficacy while reducing healthcare cost. In this investigation, we model potential cost savings associated with the use of single-fraction intraoperative radiotherapy (IORT) compared to two commonly used alternative radiotherapy approaches. Methods: A database survey was performed of female subjects undergoing breast conserving surgery (BCS) with or without sentinel lymphadenectomy at HealthCare Partners, a major IPA in metropolitan Los Angeles, CA. Subjects were identified by cross-referencing ICD-9 codes (174.0-174.9) for invasive breast cancer, CPT codes for BCS (19120, 19125, or 19301), and CPT codes for sentinel node biopsy without ALND (38500, 38525, or 38740). Calculations were based on the 2011 U.S. Medicare Fee Schedule. Treatment costs and savings were modeled assuming that patients with node-negative disease who underwent BCS were eligible for accelerated partial breast irradiation based on American Society of Breast Surgeons Guidelines (age ≥45, IDCA, DCIS, size ≤3 cm, node and margin negative). Results: A sample of 1,478 women meeting criteria was evaluated to determine the average per-patient cost of breast radiotherapy comparing three modalities: single-fraction IORT ($4,402), 5-day multi-lumen balloon brachytherapy (MLBB) (e.g., MammoSite) ($12,021), and standard 6-week whole breast external beam radiotherapy followed by a tumor bed boost (WBRT) ($8,988). IORT was approximately 49% the cost of standard 6-week WBRT and 37% the cost of MLBB. Conclusions: When eligible breast cancer patients are offered IORT as an alternative to WBRT, the expenditures from this sample may be reduced from $13.3M to $6.5M, a savings of $6.8M. Compared to MLBB, IORT may reduce radiotherapy expenditures from $17.8M to $6.5M, a savings of $11.3M. [Table: see text]
The development of the DCIS score: Scaling and normalization in the Marin General Hospital cohort.
Authors: Baehner Frederick L. , Butler Steven M , Yoshizawa Carl N. , Prasad Che , Cherbavaz Diana B. , Jamshidian Farid , Shak Steven
Published: February 2017

190

Background: In selected low-risk patients with DCIS treated with wide local excision without radiation, the DCIS score was validated as a predictor of 10 year risk of an ipsilateral breast event (IBE - recurrence of in situ or invasive carcinoma) (p = 0.02) (Solin; SABCS 2011). As part of the development of the DCIS score, scaling from 0 to 100 and determination of risk group cutoff values was done using 100 patient DCIS samples from Marin General Hospital (MGH) selected to have a wide range of tumor characteristics. Methods: 100 patient specimens diagnosed with DCIS were provided by MGH. The Oncotype DX assay was performed, normalized expression levels for the 16 cancer related genes were determined, the DCIS Score and Recurrence Score (RS) were calculated. Distributions of the DCIS score, RS, and individual gene expression levels were described overall and by tumor characteristics. Treatment and pt outcome data were not available. Results: Samples for 96 pts had sufficient tumor and were evaluable; 47% had high nuclear grade, 52% comedo necrosis, 32% tumor size >10 mm, and 9% were ER-negative by IHC. After scaling and risk group cutoff determination, the DCIS score was low risk (0-38) for 49%, intermediate risk (39-54) for 27%, and high risk (≥55) for 24% of pts (Table). The DCIS score was widely distributed within subgroups defined by each of the clinical and pathology characteristics. Proliferation gene expression levels were low in DCIS, on average, relative to prior studies in invasive breast cancer. 92% had a proliferation gene group score <6.5, the threshold used when the RS is calculated; no threshold is used in calculating the DCIS score. Conclusions: Optimal scaling and risk cutoff determination for a wide range of all clinicopathologic characteristics provides for a wide distribution for the DCIS Score. [Table: see text]
Metronomic chemotherapy (MC) in the neoadjuvant setting: Results of two parallel feasibility trials in patients (pts) with HER2 positive (HER2+) and negative (HER2-) locally advanced breast cancer (LABC) (Traq-Me and TAME).
Authors: Petry Vanessa , Leal Alessandro , Arai Roberto J. , Marinho Simone , Paiva Marcelo , Piato Jose R. , Rosa Marcio , Hoff Paulo M. , Mano Max S.
Published: February 2017

197

Background: In a previous randomized trial (SWOG 0012), MC seemed to improve pCR rates compared to standard anthracycline/taxane neoadjuvant chemotherapy (NC). We aimed to evaluate the feasibility of MC with a taxane→anthracycline schedule, which has also been shown potentially superior to the reverse sequence [J Clin Oncol 28:15s, 2010 (suppl; abstr 548)]. We also aimed to establish the feasibility of MC in combination with trastuzumab. Methods: The original accrual goal was 25 HER2+ pts and 40 HER2- pts. HER2- pts received MC consisting of paclitaxel (100mg/m2) x8 weeks followed by doxorubicin (24mg/m2) x9 weeks combined with oral cyclophosphamide (100mg/day), without G-CSF. HER2+ pts also received trastuzumab (4 mg/kg followed by 2mg/kg) concurrently with the entire CT. Objectives: Primary: To evaluate the feasibility of these schedules (defined as a febrile neutropenia [FN] rate no higher than 10%). Secondary: cardiac safety and general tolerability; efficacy as measured by objective clinical, radiological and pathologic complete response (pCR). Results: Almost all pts were staged as III (TraQme 8/9 88% and MeTo 4/11 36%). The HER2+ cohort was prematurely closed after 2 (22%) pts developed G3 pneumonitis (during the metromonic phase). Both responded to medical treatment and recovered. One pt had G2 hand-foot skin reaction (HFS) and another had G2 mucositis. The HER2- cohort was also prematurely closed with only 11 pts because of high rates of mucocutaneous toxicity (G3 HFS in 36%, G3 rash in 9%) and also due to the recent SWOG0221 negative results. There were 2 (18%) cases of FN and 3 (27%) of G4 neutropenia in this cohort, but no cases of pneumonitis. 1/11(9%) HER2- and 5/9HER2+(55%) pts had a pCR. VEGF pathway-related biomarkers were collected and will be presented at a later date. Conclusions: The proposed MC schedules proved too toxic to be considered for further clinical development. In addition, MC resulted in unexpectedly high rates of severe pulmonary toxicity when given in combination with trastuzumab. HER2+ but not HER2- pts had an impressively high pCR rate.
The dosimetric impact of supraclavicular nodal irradiation on the thyroid in patients receiving radiotherapy for breast cancer.
Authors: Ung Kim Ann , Moran Brigid , Portillo Maria , Kron Tomas , Sawyer Brooke , Herschtal Alan , Chua Boon H
Published: February 2017

198

Background: The thyroid is not routinely considered an organ at risk in supraclavicular (SC) nodal radiotherapy (RT) for breast cancer. We aim to compare the dosimetric impact of two RT planning techniques on the thyroid: (1) conventional single anterior field to encompass the SC nodal volume defined using clinical and radiological landmarks; and (2) 3-dimensional (3D)-conformal planning to encompass the SC nodal volume contoured on planning computed tomography (CT) scans. Methods: The thyroid and SC nodal volumes were contoured on the planning CT datasets of 20 patients who had RT to the breast/chest wall and SC nodes to a dose of 50 Gy in 2-Gy daily fractions. Comparison of the following dosimetric parameters between the techniques was performed: mean and maximum thyroid dose; V5, V30, and V50 (percentage of thyroid receiving ≥5, ≥30, and ≥50 Gy respectively); percentage of SC nodal volume receiving 95-107% of the prescribed dose (homogeneity index, HI); and maximum spinal cord dose. Anatomical characteristics that influenced the dose distribution were investigated. Results: The 3D-conformal planning technique significantly increased all dosimetric parameters for the thyroid (p<0.001) (Table). It improved the mean HI of the SC nodal volume (16% vs. 93.2%; p<0.001) but resulted in a higher spinal cord dose (mean maximum dose 6.1 Gy vs. 30 Gy). The thyroid volume and depth of SC nodes did not influence the differences in the thyroid doses between the two techniques. The depth of SC nodes was significantly associated with the difference seen in the HI of SC nodal volumes between the techniques (p=0.004). Conclusions: The 3D-conformal planning technique improved the dosimetric coverage of the SC nodal volume but increased radiation doses to the thyroid compared to the single field technique. The longer term clinical consequences of radiation to thyroid should be considered in SC nodal irradiation for patients with breast cancer. [Table: see text]
Are ulcerated breast cancers biologically more aggressive compared to their non-ulcerated counterparts?
Authors: Tea Muy-Kheng Maria , Pohlodek Kamil , Staudigl Christine , Fritzer Nadja , Bartova Michaela , Singer Christian F.
Published: February 2017

21

Background: Ulcerated breast carcinomas belong to the group of locally advanced breast cancers. In this study, the authors analyzed the biological presentation of ulcerated breast cancers (ULBC), examined their histo-pathological characteristics, and addressed the question whether T4b carcinomas have more aggressive phenotypes compared to their non-ulcerated counterparts (NULBC). Methods: In this case-control study the histo-pathologies of 66 patients with ulcerated locally advanced breast cancer were evaluated and compared with 132 consecutive non-ulcerated age-matched breast malignancies at the Medical University of Vienna and Comenius University School of Medicine of Bratislava. Results: The mean age in the ULBC and NULBC group was 64,86 (SD +/- 15,54) and 64,70 (SD +/- 14,11), respectively. The average tumor size at diagnosis in the ULBC group was 54.12 mm, 55% larger than in the NULBC group (p=<0.001). Furthermore, we detected statistical significantly more poorly differentiated (G3) tumors in the ULBC collection (p=0.003) and more Her-2-neu positive (p=0.035) breast cancers. In contrast, more hormone receptor positive (ER +/- PR positive) breast cancers were detected in the NULBC group (p=0.04). In addition, a total of 37.3% (n=25) patients with ULBC were diagnosed with primary metastasis. Conclusions: To our knowledge this is the first direct comparison between ULBC and NULBC.We could demonstrate that ulcerated breast cancers are characterized by more aggressive phenotypes. The observed differences of more unfavorable prognostic factors might contribute to the generally known poor prognosis of ULBC.
Can excisional biopsy be avoided for papillary breast lesions with typical benign sonographic features and concordant core needle biopsy (CNB)?
Authors: Fu Winnie , Motiuk David , Elliot Tracy , Docktor Bobbie
Published: February 2017

26

Background: The role of surgical excision in the management of papillary lesions remains controversial. Some studies have documented upgrade rates to malignancy or atypia as high as 17%. However, due to the inclusion of atypia or malignancy at percutaneous and other differences in methodology, these rates may have been over-estimated. This study was designed to determine sonographic features that can help to decide if a lesion warrants excision or standard follow-up. Methods: With institutional review board approval, we retrospectively reviewed 113 benign papillomas without atypia that were diagnosed at US-guided CNB at Foothills Medical Centre from 2005 to 2010. Surgical pathology for 62 of these lesions were assessed. Two radiologists who were blinded to the diagnosis reviewed the sonographic images to determine the likelihood of benignity. Statistical analysis was performed using chi-square and z-score tests. Results: In our study, 5.3% of benign papillomas were upgraded. The sonographic features associated with a higher likelihood of upgrade were intracystic type [LR+ 5.67, 95% CI (1.47,12)], non-periareolar location [LR+ 2.30, 95% CI (1.04,5.06)], complex echogenic pattern [LR+ 3.10, 95% CI (1.00,9.63)], and radiologist’s impression of unlikely benign (final BiRADS) [LR+ 1.48, 95% CI (1.01,1.90)]. Although no feature was statistically significant for greater likelihood of benignity, the sonographic features that may better predict benign pathology at excision include lesions <1cm in size [LR- 0.52], homogeneously solid [LR- 0.63], smooth margin [LR- 0.69] and periareolar location [LR- 0.47]. Conclusions: The management of benign papillomas diagnosed with CNB remains controversial with a lack of agreement among published articles. Our study identifies characteristic sonographic features that are associated with higher likelihood of malignancy, warranting surgical excision. Conversely, it may not be unreasonable to place patients with lesions that are stratified as low risk into standard radiographic follow-up. As the confidence intervals span 1.00 for latter, further study is necessary to confidently recommend follow-up in place of excision.
The relationship of breast density, BMI, and menopausal status in mammography and MRI.
Authors: Chun Jennifer , Refinetti Ana Paula , Leite Ana Klautau , Schnabel Freya Ruth , Hochman Tsivia , Moy Linda ,   The Breast Surgery Section of NYULMC
Published: February 2017

36

Background: Mammographic breast density (BD) is associated with a 4- to 6-fold increased risk for developing breast cancer. A previous study has shown that background parenchymal enhancement (BPE) as measured on MRI can be correlated with breast cancer risk. Being overweight or obese is also an established risk factor for breast cancer. The purpose of this study was to evaluate the relationship between BD, BPE, FGT (assessment of fibroglandular tissue with contiguous MR images), and BMI in pre- and post-menopausal women. Methods: The Breast Cancer Database at NYU Langone Medical Center was queried and a total of 187 women had completed both screening mammograms and MRIs. Variables of interest included BD, BPE, FGT, BMI, and menopausal status. BD was defined by ACR classifications 1-4. FGT was assessed on a similar scale 1-4. BPE was categorized as minimal, mild, moderate, or marked. BMI (kg/m2) was grouped as underweight (≤18), normal (19-24), overweight (25-29), and obese (≥30). Statistical analyses were performed using Spearman Correlation Coefficients and Cochran Mantel Haenszel tests. Results: The median age in our cohort was 51 years (range 22-87 years). The majority were Caucasian (71%) with early stage breast cancers (75%). There was no correlation between BD and BPE (r=0.132) and a weak correlation between BPE and FGT (r=0.312). However, there was a strong positive correlation between BD and FGT (r=0.733). After adjusting for menopausal status, these correlations remained the same. When we stratified by BMI, we found the strongest positive association between BD and FGT among women with BMI≥25 (r=0.715). Conclusions: In our cohort of newly diagnosed breast cancer patients, BD and BPE were not correlated, even after adjusting for menopausal status. This implies that BD and BPE may represent different characteristics of breast tissue and may have different implications. We found a strong correlation between FGT and BD. This association was strongest in women who were overweight and obese. FGT is a more objective and quantitative measurement of breast density and may be more useful in quantitative breast cancer risk assessment.Further studies are necessary to determine if BPE and FGT are independent risk factors for breast cancer.
Prophylactic mastectomy: The role of risk aversion.
Authors: Kruper Laura , Bhatt Meghana , London Karin , Henderson Katherine , Vito Courtney , Yim John H. , Chen Steven L.
Published: February 2017

39

Background: The rate of women undergoing contralateral prophylactic mastectomy (CPM) has increased significantly over the past decade. Large population studies have examined factors associated with the use of CPM. We studied the factors associated with CPM within our institution. Methods: A 30-question validated survey was mailed to all patients who underwent mastectomy from 1972 to 2011 and are currently receiving treatment or surveillance at our institution. Responses were analyzed to determine the factors predictive of CPM. Multivariate logistic regression methods were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for possible associations between exposures (including age at surgery, marital status, education, race, family history of breast cancer, and BRCA genetic mutation (BRCA mutation) and likelihood of CPM. Results: 368 of 691 surveys were returned. Younger age was statistically significantly associated with increased likelihood of CPM (p-trend < 0.001). Caucasian patients were 4 times as likely to undergo CPM compared to non-Caucasian patients (OR 3.95, 95%CI=1.89-8.23). Patients with a family history of breast cancer were 3 times as likely to undergo CPM as compared with those with no family history (OR 3.38, 95%CI=1.4-8.16). Married patients were also 3 times as likely to undergo CPM compared with unmarried patients (OR 3.00, 95%CI=1.39-6.52). Reporting a BRCA mutation was highly correlated with younger age, positive family history, higher level of education and marital status. Conclusions: When faced with the decision of whether to undergo a CPM, patients must assess both objective future risks and subjective feelings about those risks. These results suggest that the decision to undergo CPM is associated with known risk factors for the development of contralateral cancer such as younger age and positive breast cancer family history. In addition, multiple demographic factors including Caucasian race and married status increased the likelihood of choosing CPM. This may relate to social support as well socioeconomic status. Further exploration into societal factors that impact CPM use is warranted.
Incidence and survival among female breast cancer patients in the United States: An analysis from national registry data 2000-2009.
Authors: Huang Huan , Lang Kathy , Namjoshi Madhav , Federico Victoria , Menzin Joseph
Published: February 2017

41

Background: This study evaluated incidence and survival among breast cancer (BC) patients in the United States during 2000-2009, by cancer stage. Methods: The Surveillance, Epidemiology, and End Results (SEER) Program SEER*Stat Database was used for this analysis. SEER is an epidemiologic surveillance system consisting of population-based tumor registries designed to track cancer incidence and survival in the US. The registries routinely collect information on incident cancer cases in areas that represent approximately 25% of the US population. We evaluated age-adjusted (to the 2000 US standard population) incidence (number of cases per 100,000 population), and survival among newly diagnosed female breast cancer patients during 2000-2009, by cancer stage (localized, regional, distant and unknown/unstaged). Results: A total of 547,086 cases of female BC were reported to SEER during 2000-2009. Localized BC (average incidence rate during 2000-2009 of 77.6 cases per 100,000 population) was the most common stage among newly diagnosed patients, followed by regional (39.7), distant (6.2), and unknown/unstaged BC (3.2). Incidence rates decreased for regional (average annual change -1.3%), localized (average annual change -0.2%), and unknown/unstaged (average annual change -7.2%) BC and increased for distant BC (1.4%). One-year (five-year) survival rates averaged over 2000-2009 (2000-2005 for five-year) were 100% (97%) for localized BC, 98% (82%) for regional BC, 65% (22%) for distant BC, and 80% (55%) for unknown/unstaged BC. Both one-year and five-year survival rates were steady during this period. Conclusions: Based on US population-based registry data, the incidence and survival for breast cancer were relatively steady for localized, regional and distant BC over the most recently-available 10-year period. There is considerable room to improve survival rates for patients with regional and distant BC. Further studies evaluating the survival experience of later-stage BC patients based on other key factors, such as age, race, treatment patterns, and tumor characteristics (e.g., ER/HER2 status) are warranted.
Uptake of surgical prophylaxis in underserved, ethnic minority BRCA mutation carriers.
Authors: Macdonald Heather R. , Ricker Charite , Opper Neisha , Wong Grace G.
Published: February 2017

45

Background: Little data exist regarding uptake of surgical prophylaxis in the underserved clinical setting. This study describes acceptance of surgical prophylaxis amongst BRCA mutation carriers in a primarily Hispanic (60%) and Asian (15%) medically underserved population. Methods: An IRB-approved retrospective chart review of deleterious or suspected deleterious BRCA mutations carriers extracted clinicopathologic data, surgical history, and family cancer history. Patients younger than the recommended age of prophylaxis, undergoing active therapy, or with metastatic cancer were excluded. Results: Forty-six carriers of known or suspected deleterious BRCA mutations expressed decisions regarding prophylactic bilateral salpingo-oophorectomy and/or mastectomy. Thirty nine women identified themselves as Hispanic, 32 from Mexico. Three women were Asian, 2 African American and 1 Middle Eastern. Forty-two patients were previously affected by cancer, with a mean age at first cancer diagnosis of 42. Four patients were unaffected. Thirty-two women with a previous cancer diagnosis accepted prophylaxis: 11 RRM plus RRSO, 10 RRSO only, 11 RRM only. Three unaffected women underwent RRSO only. None of the unaffected patients chose RRM only. Presence of an affected family member younger than 35 at time of cancer diagnosis correlated with uptake of prophylactic surgery (18 accepted vs. 1 declined; p=0.01). There was a trend towards acceptance of prophylaxis among women with earlier TNM stage that did not reach statistical significance. Conclusions: More than 50% of eligible BRCA mutation carriers in this medically underserved population underwent RRM, RRSO, or both. Young family members affected with cancer positively influenced acceptance of surgical prophylaxis. [Table: see text]
Comparison of immunohistochemistry (IHC) and quantitative RT-PCR: ER, PR, and HER2 receptor status.
Authors: Christopherson Cindy , Chang Monica , Eberhard David A. , Sninsky John J. , Anderson Steven M. , Wang Alice M. , Kwok Shirley , Calhoun Benjamin
Published: February 2017

47

Background: IHC is the present standard for measuring estrogen (ER) and progesterone receptor (PR) expression for breast cancer. However, the lack of concordance between testing laboratories and the critical patient treatment decisions made with results prompted ASCO/CAP to recommend guidelines and proficiency testing requirements to ensure accuracy. Quantitative RT-PCR (qRT-PCR) is an alternative method for ER and PR testing and while concordance with IHC has been reported, additional testing is merited. This study compares ER, PR and HER2 status determined by IHC and qRT-PCR. Methods: FFPE tissues of ER(+) tumors collected and tested at the Blumenthal Cancer Center were studied. Expression levels of ESR1, PGR, and ERBB2 were determined by a multiplex qRT-PCR TaqMan assay and by the Oncotype Dx assay. Pre-established cutpoints were used to determine positivity. Only samples with qRT-PCR and corresponding IHC data were used, resulting in 144 ER, 128 PR, and 107 HER2 comparisons. ESR1 and PGR expression levels determined by the two qRT-PCR assays were also compared. Results: Of the144 IHC ER(+) samples, 142 were positive and 2 were negative by both qRT-PCR assays. All 120 IHC PR(+) samples were positive by both qRT-PCR assays. Of the 8 IHC PR(-) samples, 5 were negative and 3 were positive by both qRT-PCR assays. Of the 107 IHC HER2(-) samples, all but 2 were negative by qRT-PCR. One sample was positive by both qRT-PCR assays; one was positive by Oncotype Dx only. The expression levels determined by the qRT-PCR assays showed good correlation for ESR1 (r=0.85) and PGR (r=0.9). Conclusions: Concordance between qRT-PCR and IHC was 98.6% for ER and 97.7% for PR. Except for a single HER2 determination, there was 100% concordance between the two qRT-PCR assays. The discordant sample was HER2 (+) by multiplex qRT-PCR and “equivocal” by Oncotype Dx. Excellent correlation was also observed in the mRNA expression levels. The absence of HER2(+) and ER(-) samples are limitations of this study. These results suggest that qRT-PCR is a promising alternative method to IHC for determining hormone receptor status. Additional testing of samples with endocrine therapy outcomes including ER(-) samples would be beneficial.
The follow-up sought after diagnosis of a BRCA-1 or BRCA-2 mutation.
Authors: Chambers Karinn Marie , Armstrong Edward Joey , Flippo Teresa , Sarantou Terry , Greene Frederick L. , Brick Wendy , White Brook , Amacker-North Lisa , White Richard L.
Published: February 2017

57

Background: A woman with a known BRCA mutation has a lifetime risk for the development of breast cancer of up to 80%. Carolinas Medical Center cares for approximately 600 breast cancer patients annually with genetic testing offered to those patients whose history meets commonly established criteria. This study seeks to document the follow-up patients with BRCA mutations most commonly undertake at our facility. Methods: This study is a retrospective review of all patients who underwent genetic testing at Carolinas Medical Center and who were found to be positive for a mutation in the BRCA gene. Since 1996 our genetics group has tested 2056 individuals, of these 246 (12%) carry a mutation of the BRCA-1 and/or BRCA-2 gene. 102 of these 246 patients (41%) had no evidence of cancer at the time of genetic testing. 144 of these 246 patients (59%) did carry a diagnosis of cancer at the time of genetic testing. Results: Of the 246 patients who tested positive for a deleterious mutation in the BRCA gene 204 (83%) had documented follow-up after their diagnosis. 140 of those 204 patients (69%) had documented initial follow-up appointments to discuss their diagnosis. 63 patients of the 140 (45%) who sought initial consultation met with a surgeon. 73 of these 140 patients (52%) had their initial consultation with a Gyn/Oncologist. 3 patients had their initial consultation with a medical oncologist and the remaining patient with their primary care physician. Documentation was available for 131 of the 204 patients (64%) in regards to follow up related to their risk of breast cancer development, 129 of those patients were being followed by a high risk breast provider. 126 of the 204 patients (62%) with long term follow-up were being followed by a Gyn/Oncologist secondary to their increased risk for ovarian cancer. This data includes all patients regardless of the decisions they made concerning surveillance or prophylactic surgery. Conclusions: The majority of the patients at Carolinas Medical Center who have tested positive for a BRCA mutation have sought long term follow-up with both a high risk breast provider and a Gyn/Oncologist in regards to their increased risk for the development of both breast and ovarian cancer.
Acute care utilization (ACU) among women receiving adjuvant chemotherapy for early breast cancer (EBC).
Authors: Enright Katherine , Grunfeld Eva , Yun Lingsong , Moineddin Rahim , Dent Susan Faye , Eisen Andrea , Trudeau Maureen E. , Kaizer Leonard , Earle Craig , Krzyzanowska Monika K.
Published: February 2017

65

Background: Adjuvant chemotherapy is considered standard care for patients with lymph node (LN) positive and high risk LN negative EBC. While toxicities of chemotherapy are documented in clinical trials, the impact of toxicities on ACU at a population level is unknown. We undertook a population based study of ACU in patients undergoing adjuvant chemotherapy for EBC compared with controls. Methods: All EBC patients diagnosed 01/07 – 12/09 in Ontario, Canada, were identified from the Ontario Cancer Registry. Pt records were linked deterministically to provincial healthcare databases. All patients received ≥1 cycle of adjuvant chemotherapy. EBC cases (n = 4,718) were matched to non-cancer controls (n = 4,718) on age and geographic location. ACUs (emergency room or hospitalizations) within 30 days of chemotherapy were identified. If the primary reason for visit was a common toxicity of chemotherapy, the visit was considered chemotherapy associated (CA). All cause and CA visits were compared between cases and controls. Logistic regression models were used to identify covariates associated with ACU. Results: ACU was significantly higher in EBC pts compared with controls for both all cause (42.1% vs 9.1%, p<.001) and CA (30.7% vs 2.4%, p<.001) visits. Fever was the most common CA toxicity (22.9% vs 1.2%, p<.001). Taxanes were significantly associated with increased ACU compared with anthracycline only. Conclusions: ACU is common among EBC receiving chemotherapy and significantly higher than among controls. Interventions aimed at mitigating CA toxicity, particularly with the use of taxanes may reduce ACUs. [Table: see text]
An overview of breast medical oncology documentation through the Florida Initiative on Quality Cancer Care (FIQCC): The Phase II 2009 results.
Authors: Gray Jhanelle Elaine , Laronga Christine , Siegel Erin , Lee Ji-Hyun , Fulp William J. , Fletcher Michelle , Jacobsen Paul B.
Published: February 2017

73

Background: Following feedback provided to each site of their 2006 compliance results and enactment of improvement plans, the FIQCC re-evaluated the quality of documentation of specific quality indicators for breast cancer in the medical records of 11 participating FIQCC sites in 2009. Quality indicators were based upon ASCO, ACOS, NCCN, and expert-consensus panel recommendations. The findings were compared with 2006 results. Methods: Chart reviews from the same 2006 FIQCC sites for pre-specified Breast Medical Oncology quality indicators were performed by trained abstractors on patients first seen in 2009. The indicators included: clinical trial decisions, consent for treatment, definitive surgery after neo-adjuvant chemotherapy, published regimen dose plan, and chemotherapy selected from a published list. Statistical comparisons of 2006 and 2009 data were performed using the Pearson chi-square exact test based on Monte Carlo estimation. Results: 636 pts (99% female) [average age of 60.7 years (range 24-94)] were evaluated, with the 2009 number of cases per site ranging from 59 to 97. Significant improvements in treatment planning and administration were seen over time when comparing 2006 (n=602) to 2009 charts. This included signed chemotherapy consent (2006: 74%; 2009: 81% p=0.047), definitive surgery after neo-adjuvant chemotherapy (2006: 88%; 2009:100% p=0.017), and the planned dose being from a published list (2006: 74%;200: 84% p=0.020). Strides were also made in documenting that patients were evaluated for clinical trial enrollment (2006:13%; 2009: 21% p=0.001). Declines were seen in chemotherapy selections from an approved list (2006:94%; 2009: 82% p<0.001). Further investigations into this finding are underway and will be presented at the meeting. Conclusions: With the adoption of specific quality indicators, evaluation of a specified number of cases across multiple practices, and then providing feedback on documentation to providers and medical teams, here we demonstrate that significant improvements in medical charting and thus quality cancer care can be made.
Indirect costs associated with metastatic breast cancer.
Authors: Wan Yin , Gao Xin , Mehta Sonam , Wang Zhixiao , Faria Claudio , Schwartzberg Lee Steven
Published: February 2017

74

Background: To estimate indirect costs (sick leave [SL]/short-term disability [STDI]) associated with metastatic breast cancer (MBC) compared to early stage breast cancer (EBC)/a general population without cancer (controls). Methods: The MarketScan Health and Productivity Management database (2005-2009) was used. Adult BC patients eligible for employee benefits of sick leave and/or STDI were identified. Difference in SL and STDI days was calculated between MBC patients and their propensity score matched EBC cohort or controls during a 12-month follow-up period. Indirect costs due to SL/ STDI were estimated by multiplying leave days with daily wages (2011 Bureau of Labor Statistics). Generalized linear model was used to examine the impact of MBC on indirect costs and potential cost drivers. Results: A total of 139 MBC/432 EBC/820 controls and 432 MBC/1,552 EBC/4,682 controls were eligible for SL and STDI respectively (not mutually exclusive), with a mean age of 49/51/50 years. After matching by age, payer type, region, index year and comorbidities, no difference was found in SL days between MBC and EBC cohorts. MBC patients had more STDI days and related cost than EBC patients and controls, with higher total indirect costs (SL + STDI). MBC patients also had more SL days/cost than controls (Table). Controlling for covariates, MBC patients incurred 47% more STDI cost vs. EBC patients (p=.009). Older patients (p=.002), non-HMO payers (p<.05), or patients not receiving chemotherapy during follow-up (p<.001) were associated with lower STDI cost. MBC patients also incurred 56% (p=.01) more SL cost and 11.6 times (p<.001) more STDI cost than controls. Conclusions: Productivity loss and associated costs in MBC patients are substantially higher than EBC patients or general population. These findings underscore the economic burden of MBC from US societal perspective. [Table: see text]
The impact of 5HT3RA antiemetics on the incidence of chemotherapy-induced nausea and vomiting (CINV), treatment adherence, and delay of therapy in early-stage breast cancer (BC) patients treated with moderately/highly emetogenic chemotherapy (MEC/HEC).
Authors: Rugo Hope S. , Palli Swetha , Grabner Michael , Quimbo Ralph A. , Knoth Russell L.
Published: February 2017

75

Background: The effectiveness of 5-HT3receptor antagonists (5HTs) for the prevention of CINV is well established. Less is known about the impact of these drugs on chemotherapy adherence (AD) and preventing delayed therapy (DT). We examined the impact of palonosetron (PAL) vs. other 5HTs on CINV incidence, treatment AD and DT in early-stage BC. Methods: An observational nested case-control study was conducted using the HealthCore Integrated Research Database (HIRD). Female patients (pts) were identified by their first claim for IV MEC/HEC between 1/1/02 and 10/31/10 (index). Inclusion criteria were: ≥ 12 months health plan eligibility pre-index (baseline) and ≥ 6 months post-index (follow-up); ≥ 1 baseline claim for BC; no claim for secondary or multiple primary neoplasms; and ≥ 1 claim for 5HT during follow-up. CINV was defined using ICD-9 codes for nausea, vomiting, or related events, and use of rescue medications for 5 days after MEC/HEC. AD was defined as receiving the requisite number of cycles within the recommended NCCN timeframe. DT was defined as exceeding 2x the NCCN-recommended cycle length between MEC/HEC claims. Outcomes were assessed using descriptive analysis and multivariate logistic regression, controlling for demographics, baseline medical conditions, and index therapy. Results: We identified 682/696 [MEC] and 1,782/3,103 [HEC] pts who received PAL or other 5HTs, respectively. For PAL vs. 5HT, 33.7% vs. 49.7% (OR: 0.51; 95% CI 0.41-0.65; p<0.01) had CINV (mean 0.27 vs. 0.61 events/cycle) in the MEC group; in the HEC group, 27.3% vs. 35.7% (OR: 0.61; 95% CI 0.53-0.7; p<0.01) had CINV (mean 0.21 vs. 0.34 events/cycle). PAL users delayed MEC at a lower rate than those using other 5HTs (2.6% vs. 8.2%; OR: 0.37; CI 0.21-0.65; p<0.01) but had similar AD (41.8% vs. 37.2%; OR: 1.2; CI 0.95-1.5; p=0.12). No differences in AD or DT were found among pts on HEC. Conclusions: Among early-stage BC pts initiating a MEC or HEC agent, PAL was associated with fewer CINV events, a lower (MEC) or equal (HEC) rate of delayed therapy, and equal adherence compared to other 5HTs.
Re-assessment of surgical breast cancer quality indicators by the Florida Initiative for Quality Cancer Care (FIQCC) consortium.
Authors: Laronga Christine , Gray Jhanelle Elaine , Siegel Erin , Lee Ji-Hyun , Fulp William J. , Jacobsen Paul B.
Published: February 2017

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Background: In 2006, the FIQCC (comprised of 11 practice sites) initiated a comprehensive review of quality of care specific to breast cancer based on QOPI/NCCN/ACOS and panel consensus quality indicators. Feedback on indicator performance was provided to participating practices in 2007 to encourage quality improvement efforts. Re-assessment of adherence to the same performance indicators was conducted in 2009. Methods: Chart reviews were conducted for breast cancer patients (pts) seen by a medical oncologist at FIQCC sites in 2006(n=602) and 2009(n=636) Quality indicators included: 1) presence/completeness of pathology report; 2) documentation of surgery type; 3) documentation of sentinel lymph node biopsy (SLNB) and if SLNB positive documentation of a complete axillary node dissection; and 4) mammogram usage post surgery. Statistical comparisons of 2006 and 2009 data were performed using the Pearson chi-square exact test based on Monte Carlo estimation. Results: The median age of pts (99% female) was 60 years (range 24-94). Compared to 2006 data, improvements were made in specimen orientation (69%-2006, 78%-2009; p=0.001) and inking of margins (89%-2006, 96%-2009; p=<0.001). In clinical node negative N0 pts, SLNB was performed in 87%, up from 82%-2006 (p=0.035). Of the pts with a metastatic SLNB, 86% went on to have a complete axillary node dissection, but not statistically significant compared to 79% in 2006 (p=0.10). Compliance continues to be highly variable across practice sites with obtaining a mammogram within 14 months of surgery (79%) (p=0.002); but the range narrowed: 26%-98% (2006) and 56%-92% (2009). Significant variances also continued in 2009 across practice sites for margin orientation (p<0.001), inking of the margins (p=0.04), and performance of SLNB (p<0.001). Conclusions: The FIQCC identified quality improvement needs in multiple aspects of breast cancer care. Improvements in margin orientation/inking, use of SLNB and follow-up mammograms after definitive surgery made over the course of this initiative speak to the benefits of continual re-assessment of adherence to performance indicators to guide quality improvement.
Molecular subtyping using MammaPrint and BluePrint as an outcome predictor in U.S. breast cancer (BC) patients.
Authors: Yao Katharine , Turk Mary , Kaul Karen , Weaver JoEllen , De Snoo Femke , Stork-Sloots Lisette , Cristofanilli Massimo
Published: February 2017

9

Background: Combined use of MammaPrint and a molecular subtyping profile (BluePrint) identifies disease subgroups with marked differences in long-term outcome and response to neo-adjuvant therapy (Glück SABCS2011). The aim of this study was to evaluate the prognostic value of Molecular Subtyping using MammaPrint and BluePrint in women with early stage BC treated at U.S. institutions following National Comprehensive Cancer Network (NCCN) standard guidelines. Methods: Frozen tumor samples from 180 BC patients (TI-III, N0-Ib) median age 57 years at diagnosis (range 28-89) were suitable for hybridization on full genome array. MammaPrint and BluePrint Molecular Subtypes were determined and survival for Luminal A (MammaPrint Low Risk), Luminal B (MammaPrint High Risk), HER2-type and Basal-type patients was assessed. Patients were treated either with breast conserving therapy or mastectomy with axillary lymph node dissection between 1992 and 2005. The median follow-up is 12.7 years. 71% was ER positive and 20% Her2 positive by IHC/FISH. 58% received adjuvant endocrine therapy (ET) (excluding 13 patients unknown treatment), 64% received adjuvant chemotherapy (CT) (excluding 12 patients unknown treatment) and 33% received both. Results: 61 (34%) Patients with MammaPrint Low Risk/Luminal-type (Luminal A) showed 5-year DFS of 97% (34% received CT and 69% ET) and 50 (28%) patients with MammaPrint High Risk/Luminal-type (Luminal B) had a 5-year DFS of 98% (60% received CT and 68% ET). Patients with BluePrint Basal-type tumors (46 (26%)) had a 5-year DFS of 80% (78% received CT); HER2-type (23 (13%)) had a 5-year DFS of 78% (87% received CT without HER2 targeted therapy). Conclusions: In this retrospective study evaluating 180 US patients with early BC treated according to standard guidelines we showed how combining BluePrint with MammaPrint can detect molecularly defined subgroups of patients who are at high risk of recurrence (HER2 and Basal-type). Furthermore, we confirmed that molecularly defined Luminal type disease is associated with excellent disease-free survival. MammaPrint and BluePrint molecular and prognostic stratification should be prospectively evaluated for therapeutic selection.
Serum proteomics and ingenuity pathway analysis (IPA)-guided discovery of response markers to androgen ablation (AA) in prostate cancer.
Authors: Kohli Manish , Oberg Ann L. , Mahoney Douglas W. , Riska Shaun M , Zhang Yuji , Zenka Roman M. , Sahasrabudhe Deepak M. , Qin Rui , Carlson Rachel , Zhang Sheng
Published: February 2017

11

Background: Currently there are no serum markers of response to AA. We performed a proteome based analysis of serum from prostate cancer patients, followed by mapping of candidate markers to networks based on known molecular interactions in Ingenuity Knowledge Base (IKB). Methods: Isobaric mass tags for relative and absolute quanititation (iTRAQ) analyzed by reverse-phase liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) was performed in serum of 3 non-localized prostate cancer cohorts. The first cohort included 15 paired untreated hormone-sensitive “pre AA” and 3-month “post AA” specimens; the second included 10 “early AA failure” (median failure time: 11 months) and the third included 10 “late AA failure” specimens (median failure time: 95 months). Differentially expressed candidate proteins were identified by comparisons of (i) paired pre/post AA proteomes and (ii) post AA proteome with the combined AA failure cohorts at a False Discovery Rate of 0.2. To facilitate biological interpretation of multiple candidates identified in the comparisons, IPA was used. Candidate markers implicated in IPA networks with statistical significance were pursued in a second, independent patient cohort for association with time to AA failure using univariate Cox regression analysis. Results: Median PSA for pre/post AA first cohort were 3.15 and 0.29 ng/ml. Median PSA for the second and third cohorts were 27.3 and 4.3 ng/ml. Between post AA and AA failure cohorts, 149 proteins were differentially expressed. Between early and late AA failure 98 proteins were differentially expressed; 47 proteins were common in both comparisons. Network enrichment analysis of the 47 proteins by IPA identified four interaction networks (p<0.01), one of which highlighted a role for 17-β-estradiol (E1). Gas chromatography used for measuring 3-month post AA initiation serum E1, estrone (E2) and testosterone levels (N=38) detected high E1, E2 levels associated with longer time to AA failure (P=0.07 for E1; P=0.08 for E2) in the independent cohort. Conclusions: A global proteomic analysis identified post AA initiation serum E1, E2 levels as potential response markers, which needs validation.
The lipid metabolome of kidney cancer.
Authors: George Saby , Choi Kyoung-Soo , Miecznikowski Jeff C. , Pili Roberto , Kazim A. Latif
Published: February 2017

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Background: The commonest type of kidney cancer is CCRCC. Kidney cancer is known to accumulate lipids and a detailed knowledge of the lipid species present in these tumors could lead to a better understanding of the underlying aberrant metabolic pathways and suggest possible treatment strategies. We attempt to identify the lipidomic profile of CCRCC using a liquid chromatography MS-based approach (LC-MS). Methods: We utilized 6 fresh frozen representative samples of CCRCC and matching non-tumor areas of kidney from nephrectomy samples. Lipids and other non-polar cellular constituents were extracted from both CCRCC and control tissues by methyl-t-butyl ether /methanol. LC-MS based lipid profiling was performed on a Waters Q-ToF Premier MS coupled with Ultra Performance LC. The peak detection and alignment across all chromatograms were performed using the XCMS software (v 1.14.1, Scripps Center for Metabolomics). Statistical comparisons of the intensities of aligned peaks were performed using the XCMS-built-in Welch's t-test. The XCMS data was converted to log2 ratios (normal/tumor) in order to utilize the paired aspect of this data: each patient’s disease tissue was analyzed in conjunction with corresponding normal tissue. Significance was determined by controlling the family wise error rate (FWER) at 0.05 using a Bonferroni adjustment. All computations were performed using the R statistical software and the “limma” package. Results: The outcome of XCMS was converted to a table that contains fold change, p value and mass to charge ratio (m/z) for each peak, its corresponding retention time, and the integrated peak intensities from all samples. Controlling FWER at 0.05 using a Bonferroni scheme, we found eight statistically significant lipids. Preliminary attempts to identify the analytes included use of METLIN (Scripps Center for Metabolomics) and HMDB (Human metabolome database, Genome Alberta and Genome Canada) databases. The identified metabolites included phosphatidylcholines, cholesterol esters and triglycerides, as well as other lipid species. Conclusions: The lipid metabolomic profile varied significantly between CCRCC and control. Further studies are underway to confirm the identities and significance of the lipid species in detail.