bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic syndrome and breast cancer recurrence within the 21-gene recurrence score assay.
Authors: Muniz Jeanette , Kidwell Kelley M , Henry Norah Lynn
Published: February 2017

104

Background: The 21-gene recurrence score (RS) assay (OncotypeDX) is prognostic in stage I-II, ER+, HER2-, node negative breast cancer (BC). While RS reflects tumor gene expression its interaction with host factors including metabolic syndrome (MS) is unclear. MS conditions such as obesity have been associated with increased risk of BC and worse prognosis. The aim of this study is to determine correlations between MS conditions and RS group or BC outcomes in both pre- and post-menopausal women. Methods: We retrospectively reviewed women with stage I-II, ER+, HER2- node negative BC evaluated with RS assay treated at University of Michigan since 2005. Demographic, pathologic and treatment data, MS criteria and menopausal status were abstracted from medical records. MS was defined as ≥ 3 of the following within 6 months of diagnosis: BMI ≥ 27.7kg/m2; hypertension (HTN); impaired fasting glucose (IFG); HDL < 50mg/dL; hypertriglyceridemia (trig). RS groups were defined as low ( < 18), intermediate (18-30) and high ( > 31). Results: Of 533 eligible women 74% had stage I disease and 61% were postmenopausal at diagnosis. MS criteria prevalence was 43% BMI, 42% HTN, 34% trig, 14% IFG and 13% HDL. MS was present in 22% and more common in post- vs pre-menopausal women (30% vs 9%; p < 0.0001). RS groups were 55% low, 38% intermediate and 7% high. There was no significant association between RS group and overall MS status or any individual criterion, controlling for stage, and no association after stratification by menopausal status. Postmenopausal status was associated with higher RS group (p = 0.039), independent of stage. Over the 4.2 year median follow-up there were 7 deaths and 20 events, including 5 DCIS, 3 local and 11 distant recurrences and 1 second primary BC. There was insufficient power to detect associations between event rate and MS status. Conclusions: MS and comprising conditions are present in many early stage breast cancer patients, especially postmenopausal women. We were unable to identify associations between RS group and MS criteria. Thus the known worse BC prognosis with MS is not reflected in the RS. Identification of factors underlying this higher risk will be important for optimizing management of patients with breast cancer and MS.
Motivation and mortality in geriatric patients with early stage breast cancer.
Authors: DuMontier Clark , Clough-Gorr Kerri , Silliman Rebecca A , Moser André
Published: February 2017

105

Background: Evidence suggests that an older patient’s motivation and life outlook are associated with health outcomes. A measure of motivation called the Getting Out of Bed Scale (GOB) was previously validated in a cohort of geriatric patients with early stage breast cancer. The aim of our project was to assess the association between GOB and mortality, both all-cause and breast-cancer specific, using the same dataset. Methods: We evaluated 660 women ≥ 65-years old diagnosed with stage I-IIIA primary breast cancer in four geographic regions in the US. Data were collected over ten-years of follow-up from consenting women’s medical records, telephone interviews, National Death Index, and Social Security Death Index. To address attrition bias, a multiple imputation approach using two-fold fully conditional specification was used to generate a complete dataset and allow for sufficient power in our statistical testing. Results: Using this dataset, a cox regression survival analysis found no significant association between GOB and mortality, both all-cause [5 years HR (95% CI): 0.76 (0.50,1.15), 10 years: 0.77 (0.59, 1.01)] and breast-cancer-specific [5 years: 0.92 (0.48, 1.73), 10 years: 0.84 (0.53, 1.33)]. This observation held true even after adjustment for other validated health-related quality of life measures of mental health, physical functioning, and socioeconomic status. Notably, patients with high mental health scores as measured by the Mental Health Index Short Form had significantly lower mortality, both all-cause [5 years: 0.42 (0.27, 0.65), 10 years: 0.59 (0.44, 0.79)] and breast-cancer specific [5 years: 0.42 (0.20, 0.90), 10 years: 0.52 (0.31, 0.89)]. Conclusions: These results suggest that GOB does not predict mortality in geriatric patients with early stage breast cancer; however, more research is needed to assess hope and outcomes in geriatric cancer patients. This study would not have been possible without the multiple imputations approach, which allows for greater power in researching longitudinal datasets that would otherwise suffer from loss to follow up.
Effects of chemotherapy on quality of life in breast cancer survivors.
Authors: Wandell Kaitlin K. , Lustberg Maryam B. , Reinbolt Raquel E. , Orchard Tonya , Andridge Rebecca , Wandell Hayley , Schade Carly , Moran Tim , Yang Nan , Conlan Trisha
Published: February 2017

112

Background: Women undergoing chemotherapy for breast cancer often experience side effects that can impact quality of life and tolerance of planned therapy. This can lead to poor outcomes. By understanding these changes, we can intervene and improve the treatment for women. We hypothesized that chemotherapy would be associated with changes in functional status and nutrition related symptoms in breast cancer survivors. Methods: Patients were prospectively recruited prior to initiation of their neo-adjuvant or adjuvant therapy. Body mass index (BMI) was abstracted from records. The patient’s functional status was assessed using the Duke Activity Status Index (DASI), and the Patient Generated Subjective Global Assessment (PG-SGA) characterized nutrition-related symptoms of patients. Participants completed these questionnaires prior to initiating the first cycle chemotherapy (time point 1), during the second cycle (time point 2), and during the last cycle of chemotherapy, 12-20 weeks after initiation of treatment (time point 3). Changes in BMI, functional status, and symptomatology were analyzed using linear mixed effects models. Results: Twenty-five women enrolled; 19 women with a median age of 51 (range 33-66) completed the study. There was no significant change in BMI (p = 0.18) over the duration of chemotherapy. Analysis of DASI data indicated that there was a significant decline in peak oxygen uptake (p = 0.005), showing a decrease in functional capacity from before the first cycle to both the second and the last cycles. This suggests that functional capacity dropped significantly once chemotherapy began and stayed below baseline. There was also a significant change in PG-SGA (p = 0.005), indicating significant reported nutrition-related symptoms. PG-SGA scores were significantly higher during the second cycle compared to the other two time points, indicating that patient’s showed the highest degree of symptoms shortly after initiation of treatment and then improved. Conclusions: Chemotherapy is associated with symptomatology and a decrease in functional capabilities. Improved understanding of symptom burden during chemotherapy will allow more specific interventions to be designed that can help improve quality of life.
Online video support group pilot: Connecting young women diagnosed with breast cancer.
Authors: Taylor Nicole Anne , Esser Michelle , Atkinson Lori , Sutliff Medha , Stephens Christina , Rowe Jean , Ajango Mary
Published: February 2017

113

Background: Young Survival Coalition (YSC) is the premier global organization dedicated to the critical issues unique to young women and breast cancer. Young breast cancer survivors (YBCS) have a strong desire to connect in-person with other young survivors although location, timing of meetings and illness can deter in-person meetings. YSC sought to create a programmatic initiative where YBCS can connect online through video to “see” and support each other as well as reduce a sense of isolation. Methods: YSC initiated an 8 month online video support group pilot, with six groups meeting monthly. Two groups focused on specific populations: under age 30; and YBCS with metastatic breast cancer. A YSC staff person provided technology support at the start of each meeting. A paid facilitator or a peer volunteer led each meeting. A variety of technology platforms were tested, with “GoToMeeting” being the most reliable and the most commonly used. Results: Approximately 29 YBCS participated regularly across the six groups. Post-meeting and post-pilot evaluations were strongly positive. Eighty percent felt their concerns were addressed during the meetings and being able to “see” other YBCS helped to build community and add to the support received. The top reason for participating in the support group was to connect with other YBCS (70%). The topics of most interest were sex and intimacy and anxiety (tied) followed by discussion of side effects. A little over half of the respondents (54%) reported wanting a facilitator to lead the groups instead of a peer. Seventy-three percent said they would participate in online video support groups again if offered. A text message reminder of the upcoming support group meeting, received a day prior to the meeting, was preferred over email. Conclusions: YSC’s online video support group program is a viable and innovative method of connecting YBCS, by providing the opportunity to give and receive support in the comfort of their own home. This pilot provided YSC the information needed to move into a second stage of program implementation and evaluation.
The effect of neoadjuvant chemotherapy on short-term outcomes in breast surgery: A propensity score adjusted analysis of NSQIP data.
Authors: Cordeiro Erin , Arnaout Angel , Cil Tulin
Published: February 2017

115

Background: Neoadjuvant chemotherapy (NAC) is increasingly used in the treatment of breast cancer. The primary objective of this study was to determine whether administration of NAC increased the proportion of overall 30-day post-operative complications among patients undergoing surgery for invasive breast cancer. Methods: An analysis of the American College of Surgeons, National Surgical Quality Improvement Program (ACS-NSQIP) participant user files from 2005-2012 was performed. Patients undergoing surgery for invasive breast cancer were included; those with high-risk comorbidities or concurrent surgery were excluded. The primary outcome was a composite of overall 30-day post-operative complications. A propensity score was calculated and a propensity score adjusted multivariable logistic regression model was used to determine the independent effect of NAC on overall 30-day complications. Results: In the study period67,685 patients having surgery for invasive breast cancer were identified; of those, 3,624 (5.5%) received NAC. The rate of NAC use within this cohort increased from 5.5% to 10.2%. Patients who received NAC were: younger and had fewer medical comorbidities, but, were more likely to receive neoadjuvant radiation and undergo bilateral surgery. On unadjusted analysis, patients receiving NAC had significantly more post-operative complications than those not receiving NAC (4.9% vs. 3.7%, p = 0.0003) mainly due to infection and bleeding. However, after adjusting for confounders by propensity score adjusted multivariable regression, there was no longer a significant difference in overall 30-day post-operative complications between those receiving NAC versus not (odds ratio 1.16 [95%CI: 0.98, 1.36]). Conclusions: This is the largest study to examine the effect of NAC on post-operative complications in patients undergoing surgery for invasive breast cancer. The receipt of NAC does not impart a significantly increased risk of post-operative complications in this patient population.
Usefulness of digital breast tomosynthesis (DBT) in evaluation of pathological response after neoadjuvant chemotherapy (NAC) for breast cancer.
Authors: Arasaki Ayano , Uchiyama Nachiko , Kinoshita Takayuki
Published: February 2017

119

Background: Digital breast tomosynthesis (DBT) has been developed recently and it provides an advantage in detection of breast masses compared to 2D mammography (MMG) since it allows to separate the tissue layers and to noticeably reduce occlusions caused by overlapping anatomical structures. Neoadjuvant chemotherapy (NAC) has been used increasingly for the treatment of breast cancer. The imaging methods that have been used until now to assess tumor response to NAC have serious limitations. Attaining pathological complete response (pCR) is the most important predictor of long-term survival in patients receiving NAC. We assessed the radiological findings and capability of DBT to predict response to NAC in comparison with 2D MMG. Methods: 33 woman (mean age, 47.3 y.o.) having 36 lesions were recruited. Image utilizing adjunction of DBT to 2D MMG were taken for diagnosis from January, 2010 to March, 2015. Pathological subtypes were IDC (n = 34), ILC (n = 1), and IMPC (n = 1). Pathological responses of the lesions to NAC were Grade1 (n = 16), Grade2 (n = 11), and Grade3 (n = 9). The clinical image data sets were acquired with a DBT system (MAMMOMAT Inspiration, Siemens, Germany).For each patient, CC and MLO views were taken for diagnosis. With one-view 2D MMG and DBT, those radiation dose, utilizing the ACR phantom 156, were 1.20mGy and 1.80mGy. Results: The clinical response to NAC was classified into the following categories: 1) Fairly Response (FR): reduction in size of the tumor by more than 70% including Complete Response (CR), 2) Partial Response (PR): reduction in size of the tumor by 30% or more but less than 70%, 3) Stable disease (SD): reduction in size of the tumor by less than 30%. DBT findings of pathological Grade2-3 cases were all suggested FR (28/28, 100.0%) Grade3 cases were all suggested CR (9/9,100.0%). Regarding the Grade1b cases, all lesions were suggested PR (8/8, 100.0%). Regarding the Grade1a cases, 3 out of 8 (36.5%) lesions were suggested CR, and 2 out of 8 (25%) lesions suggested PR, and 3 out of 8 lesions suggested SD. Conclusions: DBT will contribute to improved diagnosis accuracy with regard to NAC response to breast cancer in comparison with 2D MMG.
Eribulin and carboplatin in heavily pretreated patients with metastatic breast cancer: A single institution experience.
Authors: Martin Romano Patricia , Baraibar Iosune , Fernández-Hidalgo Oscar , Santisteban Marta , Espinós Jaime , Salas Diego , Sala Pablo , Gardeazabal Itziar , Zubiri Oteiza Leyre , Aramendia Jose M.
Published: February 2017

122

Background: In recent years many drug combinations have demonstrated clinical activity in heavily pretreated patients (pts) with metastatic breast cancer (MBC). Eribulin (E) in monotherapy has shown a beneficial effect in overall survival (OS) with slight rate of objective responses (OR) and poor effect in progression free survival (PFS). The Eribulin – Carboplatin (Cb) combination has been studied in other types of tumors in a phase Ib with promising results. We initiated an exploratory program with an off-label combination of E – Cb in pts with visceral disease and ECOG < 2. Methods: We retrospectively analyzed pts with MBC previously treated with anthracyclines, taxanes, and Capecitabine. Chemotherapy regimen consisted of E 1.1mg/m2 on days 1 and 8 and Cb AUC: 5 on day 1 every 21 days. Toxicity was assessed according to CTC criteria v 4.0. OR, PFS and OS rates were also evaluated. RECIST criteria were used to appraise radiological response. Results: Treatment was delivered in 10 pts. Median (M) age was 56 (range, 39-65). Pts characteristics were defined as follows: ECOG 0 (1 pt), 1 (6 pts) and 2 (3 pts); histological subtypes: luminal 9 pts and Her-2, 1 pt. M of previous lines was 7 (3-11). M of metastatic localizations were 3 (1-4). M of administered cycles was 6’5 (1-10). Grade 2 toxicity was asthenia 40%, peripheral neuropathy 10% and nausea - vomiting 10%. G 3 anemia and thrombopenia were noted in 20%. G 3-4 neutropenia was observed in 5 pts. Two pts required hospital admission due to febrile neutropenia. OR rate: complete response 10%, partial response 50% and stable disease 40%. Biochemical response rate was 80%. M of follow-up was 11 months, with M PFS and OS of 8 (4-11) and 18 months (4-18) respectively. Conclusions: Eribulin and Carboplatin is feasible, achieving remarkable response and survival rates with an acceptable toxicity profile in heavily pretreated patients with metastatic breast cancer. Preliminary results are promising and encourage us to continue recruiting patients.
Lymph node ratio as prognostic after neoadjuvant therapy in breast cancer.
Authors: Bertoni Danielle Marie , Hernandez-Boussard Tina , Wapnir Irene
Published: February 2017

123

Background: Lymph node ratio (LNR) is defined as the proportion of involved nodes over total number of nodes. The latter may be superior to TNM staging as a prognostic indicator in breast cancer treated surgically first. Pathological staging after neoadjuvant therapy (NAT) is based on the residual cancer burden (RCB) in breast and nodes. We hypothesized that LNR after NAT offers additional useful prognostic information. Methods: Patients receiving NAT were identified through the Stanford Tumor Registry. Based on previously published classifications LNRs in node positive disease was classified as low (L) 0.01-0.2, intermediate (I) 0.21-0.65, and high (H) > 0.65. Other discriminant cut-off points were sought. Kaplan-Meier log-rank test was used for survival analysis. Results: 105 node-negative and 92 node-positive cases were identified (2003 -2010). Median number of nodes examined was 13, range 2-40. LNR among the node-positive cohort varied from 0.03 to 1.0. The distribution of positive nodes for L was 1-4, for I 1-13, and for H 2-25. The 3-year DFS and OS were 94% and 98%, for node-negative cases, and 66% and 77% for node-positive cancers. Survival for L = 79% (median 55%); I = 56.2% (median 52%); and H = 55.6% (median 49%). Using 0.5 as a new discriminant, the 3 and 5-year OS for LNR < 0.5 was 78.1% and 69.9%, and for LNR > 0.5 was 52.2% and 39.8%, respectively (p = 0.02). Conclusions: LNR of 0.5 was found to discriminatefor survivalin patients after NAT. This differs from the LNR categories defined for patients who had surgery first. Further validation in larger dataset is warranted.
Investigations of breast cancer screening using a novel in vitro diagnostics technology.
Authors: Tao Hongmei , Du Xuedong , Tang Xing , Lin Yue , Lou Da , Yu Chris Chang
Published: February 2017

13

Background: A newly developed in-vitro diagnostic technology named Cancer Differentiation Analysis Technology (CDA) was investigated for breast cancer screening. The CDA technology is a blood-sample based, multi-level, multi-parameter diagnostic method which detects signals from both proteins and cells, in which multiple aspects and parameters of information were collected to improve diagnostic accuracy. Methods: Blood samples from breast cancer group (n = 222), and control subjects (n = 204) were collected in EDTA tubes. CDA values were measured using a CDA medical device. The results were shown in Table 1 and Figure 1 below. Results: The average CDA values of breast cancer and control groups were 50.43 and 34.03 (rel. units) respectively. The results indicated that breast cancer could be significantly distinguished from the control (p < 0.001). Area under ROC curve was 0.914. When Youden Index reached the maximum, sensitivity and specificity was 82.0% and 89.2% respectively. Conclusions: Initial results showed that CDA technology could be a potential candidate for breast cancer screening. [Table: see text]
The synergistic effect between celecoxib and luteolin and dependence on estrogen receptor in human breast cancer cells.
Authors: Jeon Ye-Won , Suh Youngjin
Published: February 2017

135

Background: The anti-cancer effects of celecoxib and luteolin are well known. Although our previous study demonstrated that the combination of celecoxib and luteolin synergistically inhibits breast tumor growth compared with each of the treatments alone, we did not uncover the molecular mechanisms of these effects. The aims of our present study were to compare the effects of a celecoxib and luteolin combination treatment in four different human breast cell lines and to determine the mechanisms of action in vitro and in vivo. Methods: Using MCF-7, MCF7/HER18, MDA-MB-231 and SkBr3 human breast cancer cells, proliferation assay, apoptosis assay, inhibition assay with MEK and PI3K inhibitor in addition to western blotting and xenograft study after treatment with celecoxib and luteolin. Results: The synergistic effects of a celecoxib and luteolin combination treatment yielded significantly greater cell growth inhibition in all four breast cancer cell lines compared with the single agents alone. In particular, combined celecoxib and luteolin treatment significantly decreased the growth of MDA-MB-231 cancer cells in vivo compared with either agent alone. The celecoxib and luteolin combination treatment induced synergistic effects via Akt inactivation and extracellular signal-regulated kinase (ERK) signaling inhibition in MCF-7 and MCF7/HER18 cells and via Akt inactivation and ERK signaling activation in MDA-MB-231 and SkBr3 cells. Conclusions: These results demonstrate the synergistic anti-tumor effect of the celecoxib and luteolin combination treatment in different four breast cancer cell lines, thus introducing the possibility of this combination as a new treatment modality.
Neoadjuvant chemotherapy with docetaxel, carboplatin, and weekly trastuzumab (TCH) activity in HER2-positive early breast cancer: Results after a median follow-up of 4.5 years.
Authors: Kolberg Hans-Christian , Akpolat-Basci Leyla , Stephanou Miltiades , Hannig Carla , Liedtke Cornelia
Published: February 2017

140

Background: Most patients with HER2-positive receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline containing regimes. Previous investigations on neoadjuvant treatment with TCH showed pCR-rates in the range of 40%, however, survival data have not yet been presented. Here we present 4.5-year follow-up data for a cohort of 51 patients treated with neoadjuvant TCH. Methods: We treated 51 patients with operable HER2-positive breast cancer with a neoadjuvant schedule of docetaxel (75 mg/m2) and carboplatin (AUC 6) q3w and trastuzumab (2(4)mg/kg) q1w. Lymph node involvement was verified by SLNB or core-cut-biopsy. Mean age at diagnosis was 55 years, 68.6% had ER positive tumors, 39.2% presented with grade 3 disease and 49% of patients were node-positive. Patients were monitored by ultrasound. After 6 cycles of chemotherapy all patients had surgery. Axillary dissection was performed in case of positive lymph node status prior to TCH. After surgery trastuzumab was continued q3w up to one year. Results: Side effects were mild, no grade III/IV toxicities occurred and no case of cardiomyopathia was observed. 21 (41.18%) patients achieved a pCR, 18 (72.0%) patients converted from cN+ to ypN0. Outcome data at a median follow-up of 53.6 months are as follows (see table). Conclusions: Outcome following neoadjuvant TCH as observed in our analysis compares well to outcome data observed in adjuvant trastuzumab trials such as HERA or BCIRG006. Particularly among patients with ER positive disease and those experiencing axillary conversion we observed an excellent outcome. Importantly, TCH was well tolerated in our cohort. Therefore our data support the use of TCH as neoadjuvant therapy regimen for patients with HER-positive breast cancer. [Table: see text]
Correlation between Oncotype Dx score with histologic grade, tumor size and Ki67 in patients with early stage breast cancer: A single academic institution experience.
Authors: Lathrop Kate Ida , Mazo- Canola Marcela , Gelfond Jonathan , Hinojosa Barbara , Shiao Jay C , Terracina Katherine A
Published: February 2017

146

Background: Oncotype DX is an RT-PCR based assay that calculates a recurrence score (RS) to predict chemotherapy benefit in patients with breast cancer. Some authors have proposed using Ki-67, receptor status, Nottingham grade, and tumor size as histo-pathologic variables that could potentially substitute for the RS. Comprehensive and larger reviews are still lacking in this filed. To our knowledge this is the largest retrospective review of cases in a single academic institution. Methods: We retrospectively reviewed and reported baseline patient demographic characteristics (including age, race and gender) and routine pathological features such as histologic grade, Ki-67, tumor size, and histologic type. All patients included in this study had an Oncotype Dx ordered between 2007 and 2014. Results: Our analysis included 252 patients of which 248 were females and 4 were males, median age was 56, median tumor size of 2.1 cm. The majority of cases were grade 2 with 49.4%, followed by grade 3 with 28.1% and grade one represented 22.5% of the sample. Ki-67 ranged from 2-98 %. Three variables correlated significantly with Oncotype Dx: tumor size (p = 0.0115), Ki-67 (p = 1.509e-09) and grade (p = 0.0307). Using these three variables together, the percentage of variance on the Oncotype Dx score was 0.35 (R2- coefficient of determination). Conclusions: While tumor size, grade and Ki-67 individually correlate significantly with Oncotype Dx score, taken together, they cannot reliably predict the RS. Also, the capability of these three factors to predict the RS decreases for tumors with high RS. Therefore, we conclude the RS can provide additional valuable information and should not be replaced by analysis of routine histologic variables alone.
Towards intraoperative microCT imaging of breast cancer resections.
Authors: Salmon Phil , Sasov Alexander
Published: February 2017

147

Background: MicroCT analysis of breast cancer resections was shown by Rong et al. [Tang R et al. (2013) The Breast Journal 19(5), 485-489; Tang R et al. (2013) Breast Cancer Research and Treatment 139(2), 311-316] to attain equivalence with pathology-histology in the assessment of positive margin. However, Rong et al. noted that the 14 minute scan cycle time–7 minutes scan, 7 minutes reconstruction–was a potential limitation. Methods: This paper reports the development of microCT instrumentation and software to address this and other technical challenges. These include (a) reducing the scan-reconstruction time, (b) a small desktop footprint, (c) reconciling optimal soft tissue contrast with minimizing artefacts from inserted metal wires and large calcifications, and (d) features to aid hospital workflow such as a barcode reader, an optical camera to photograph the specimen, and process automation. Scans were done with the purpose-built SkyScan1275 table-top microCT scanner, on frozen anonymous archived breast cancer resection samples. Results: Minimum scan time retaining acceptable image quality was 3 minutes. Reconstruction time was reduced to less than a minute by PC graphics accelerators. Scan-reconstruction cycle time can thus be < 4 minutes. A small (105 x 64 cm) desktop footprint with a weight of 160 kg, requiring only a sturdy laboratory desk, has also been attained in this scanner. Artefacts from large calcifications and metal wires were reduced to non-obtrusive levels by scanning with 1mm aluminum filter and software techniques. An automated scan sequence was developed with sample holders recognized electronically in the scanner. On pressing a single button, the scanner automatically goes to the appropriate magnification and sample height, scans the sample, then reconstructs the scan with preset parameters, and finally opens the reconstructed dataset in software for interactive volume-rendered viewing. Sample barcode reading and optical photo taking can be included in this auto-scan sequence. Conclusions: These developments bring microCT nearer to realizing its potential as an intraoperative “back-table” technique in breast cancer surgery to obviate revisions and improve the surgery process and outcome.
The SSO/ASTRO Consensus on Breast Margins: Has it affected clinical practice?
Authors: Cate Sarah P. , Greenberg Arielle Brooke , Bassin Leah , Gillego Alyssa , Chadha Manjeet , Aharonoff Gina , Boolbol Susan K.
Published: February 2017

148

Background: Adequate margin width remains a subject of much controversy in breast conserving surgery. The Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO) presented a consensus statement on margins in December 2014. This guideline stated that re-excision is recommended only in cases where tumor is present on inked margin. In this study, we sought to determine the consensus statement’s impact on re-excision practices at our institution. We examined re-excision rates eleven months before the release and 17 months after the release of the statement. Methods: Patients included in this IRB approved study had a diagnosis of invasive breast carcinoma, underwent breast conserving surgery, and were treated with adjuvant radiotherapy. Patients with pure DCIS were excluded. Results: One hundred and two women treated from January to November 2013 were included in the pre-consensus group. One hundred and three women were treated from December 2013 to May 2015 in the post-consensus group. The women treated prior to the consensus statement (n = 102) and those women treated after the statement (n = 103) were equally matched in terms of patient age, hormone positivity, and tumor size. A close margin at our institution is defined as < 2mm from the tumor edge. There were 16/102 women prior to the consensus who had close margins and 32/103 women in the post-consensus group. Of these, 68.8% (11/16) underwent re-excision for close margins in the pre-consensus group compared to 3.1% (1/32) after the consensus statement was released (p value < 0.01). Conclusions: The rapid adoption of the SSO/ASTRO margin consensus statement at our institution, although not statistically significant, led to a decrease in the number of patients who underwent a re-excision for close margins. Women with a close surgical margin were less likely to undergo additional surgery for re-excision after the guidelines were released. In our institution, using a standard criterion for re-excision, the re-excision rate for close margins decreased from 68.8% to 3.1%. Further studies are needed to examine the impact of the consensus statement on re-excision practices in a larger group of patients.
Phase III randomized, placebo-controlled trial of carboplatin (C) and paclitaxel (P) with/without veliparib (ABT-888) in HER2- BRCA-associated locally advanced or metastatic breast cancer (BC).
Authors: Huggins-Puhalla Shannon Leigh , Han Hyo S. , Diéras Véronique , Friedlander Michael , Somlo George , Arun Banu , Wildiers Hans , Kaufman Bella , Ayoub Jean-Pierre M. , Shah Melissa , Burmedi David , Qin Qin , Qian Jane , Giranda Vincent L. , Shepherd Stacie Peacock
Published: February 2017

155

Background: BRCA-mutated tumors are more susceptible to platinum therapy and PARP inhibitors due to underlying defects in homologous recombination repair of DNA damage. In preclinical models the potent oral PARP1/2 inhibitor veliparib was shown to enhance sensitivity to C and to have single-agent activity in BRCA+ cell lines. Phase 1 trials suggest promising antitumor activity and acceptable toxicity of veliparib plus C/P in triple-negative BC (Puhalla et al. Cancer Res 2012;72:PD09-06) and single-agent activity of veliparib in BRCA+ BC (Somlo et al. J Clin Oncol 2014;32:abstr. 1021). This phase III trial assesses efficacy and toxicity of veliparib plus C/P vs C/P alone in patients with HER2− BRCA-associated locally advanced or metastatic BC (NCT02163694). Methods: Phase III randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients (female or male; ≥ 18 years) have HER2−metastatic/locally advanced unresectable BC with (suspected) deleterious BRCA1/2 germline mutations and received 2 or fewer prior lines of DNA-damaging chemotherapy for metastatic BC. In addition, patients must have received ≤ 1 prior line of platinum therapy (any setting) without progression within 12 months of completing treatment. Patients are randomized 2:1 to C/P with veliparib or C/P with placebo, stratified by estrogen and/or progesterone receptor expression, prior platinum therapy, and central nervous system metastases. Veliparib (120 mg p.o. BID) or placebo will be given on Days −2 to 5, C (AUC 6 mg/mL/min i.v.) on Day 1, and P (80 mg/m2i.v.) on Days 1, 8, and 15 (21-day cycles). Treatment continues until unacceptable toxicity or progressive disease (PD). Patients in the placebo arm who discontinue due to PD are eligible for crossover to veliparib monotherapy. The primary objective is to assess if the addition of veliparib to C/P increases progression-free survival; additional objectives include evaluation of overall survival, clinical benefit rate, objective response rate, quality of life, and safety. Enrollment began in July 2014 with a planned sample size of 270 patients. Clinical trial information: NCT02163694.
Benefits and safety of multigene panel testing in patients at risk for hereditary breast cancer.
Authors: Kapoor Nimmi S. , Curcio Lisa D. , Blakemore Carlee A. , Bremner Amy K. , McFarland Rachel E. , West John G. , Banks Kimberly C.
Published: February 2017

16

Background: Recently introduced multi-gene panel testing including BRCA1 and BRCA2 genes (BRCA1/2) for hereditary cancer risk has raised concerns with the ability to detect all deleterious BRCA1/2 mutations compared to older methods of sequentially testing BRCA1/2 separately. The purpose of this study is to evaluate rates of pathogenic BRCA1/2mutations and variants of uncertain significance (VUS) between previous restricted algorithms of genetic testing and newer approaches of multi-gene testing. Methods: Data was collected retrospectively from 966 patients who underwent genetic testing at one of three sites from a single institution. Test results were compared between patients who underwent BRCA1/2testing only (limited group, n = 629) to those who underwent multi-gene testing with 5-43 cancer-related genes (panel group, n = 337). Results: Deleterious BRCA1/2 mutations were identified in 37 patients, with equivalent rates between limited and panel groups (4.0% vs 3.6%, respectively, p = 0.86). Thirty-nine patients had a BRCA1/2 VUS, with similar rates between limited and panel groups (4.5% vs 3.3%, respectively, p = 0.49). On multivariate analysis, there was no difference in detection of either BRCA1/2 mutations or VUS between both groups. Of patients undergoing panel testing, an additional 3.9% (n = 13) had non-BRCA pathogenic mutations and 13.4% (n = 45) had non-BRCA VUSs. Mutations in PALB2, CHEK2, and ATM were the most common non-BRCA mutations identified. Conclusions: Multi-gene panel testing detects pathogenic BRCA1/2 mutations at equivalent rates as limited testing and increases the diagnostic yield. Panel testing increases the VUS rate, mainly due to non-BRCA genes. Patients at risk for hereditary breast cancer can safely benefit from upfront, more efficient, multi-gene panel testing.
Outcomes of retesting BRCA-negative patients using multigene panels.
Authors: Yadav Siddhartha , Fulbright Jennifer , Dreyfuss Heidi , Reeves Ashley , Campian Sarah , Thomas Vicky , Zakalik Dana
Published: February 2017

23

Background: New technologies for identifying hereditary predisposition to breast cancer have led to the discovery of novel genes associated with cancer risk. This has prompted re-evaluation of patients who previously tested negative for BRCA1/2 gene mutations, with a possibility of discovering new genes which may impact management. This study reports on the results of retesting patients who previously were negative for BRCA1/2. Methods: Patients who tested negative for BRCA1/2 mutations who had significant personal and family history were referred back to the Cancer Genetics Center between February 1, 2012 and May 30, 2105 for discussion of additional testing. A detailed personal and family history was reviewed, and patients were counseled about the genetics and clinical implications of panel testing for multiple breast cancer genes. Panel testing using next generation sequencing technologies was ordered. Patients were seen in follow up for discussion of results and management. Results: A total of 12 pathogenic mutations were identified during the study period. The genes and frequencies of these mutations were: CHEK2(3), PALB2(3), ATM(2), APC(1), BARD(1), CDH(1), MUTYH(1). There were 33 variants of undetermined significance(VUS) in 27 patients. 5 of these were seen in patients with a known pathogenic mutation; 3 others were later classified as benign. The frequencies of these VUSs were: ATM (9), PALB2(3), BARD1 (3), PTEN(3), PMS2(3), MSH6(2), CHEK2 (1), MYH(1), RAD51(1), BRIP1(2), NF1(1), BMPR1A(1). Of the 46 patients who had their initial BRCA testing and repeat panel testing between February 1, 2012 and May 30, 2015, 6 (13%) tested positive for a pathogenic mutation. Conclusions: This study demonstrates the feasibility and potential clinical benefit of retesting individuals who previously tested negative for BRCA1/2 mutation. This approach had a significant management impact on patients and their families, with a 13% detection rate of pathogenic mutations. The success of retesting is predicated upon an infrastructure of provider and patient education, pre and post genetic counseling and serves as a model for other centers.
Neutrophil lymphocyte ratio (NLR) change after systemic treatment as a predictive factor of cancer specific survival in stage IV breast cancer.
Authors: Shin Hae-na , Kim Jisun , Kim Hee Jeong
Published: February 2017

29

Background: Inflammatory response exacerbates mechanisms linked to tumor growth and dissemination. As an index of systemic inflammatory status, neutrophil lymphocyte ratio (NLR) may be a predictive biomarker of both prognosis and response to therapy. We evaluated initial pre-treatment NLR and post-treatment NLR change to assess whether initial and change in NLR would be predictive of disease outcome in stage IV breast cancer patients. Methods: This study included 250 stage IV breast cancer patients diagnosed at Asan Medical Center between 1997 and 2012. The NLR was calculated from the differential count by dividing neutrophil percentage by lymphocyte percentage. All initial (pre-treatment) NLR was evaluated at the first visit day in Asan medical center. Post-treatment NLR was obtained at the first follow-up visit at the outpatient department after first treatment (chemotherapy first: about after 3weeks/endocrine therapy: after 3~6 months). The initial (pre-treatment) NLR was divided by quartile, and the NLR change was calculated by dividing post-treatment NLR by pre-treatment NLR. If the value was ≥ 1.2, NLR change was increased; if not, it was not changed or decreased. We evaluated prognostic value of NLR by comparison with Cancer Specific Survival (CSS). Results: When comparing pre-treatment NLR and post-treatment NLR, the NLR was increased in 85 patients (34%) and stationary or decreased in 165 patients (66%). There was no significant difference between two groups in baseline characteristics. On the other hand, in CSS, the difference between two groups are shown, but does not have statistical significance (log rank p = 0.052). The 1, 3, 5 year CSS rate was 78.8%, 35.7%, 20.5% in increased NLR group, and 87.1%, 49.3%, 26.9% in the other group. Multivariate analysis suggested that increased NLR change (Post/Pre NLR ≥ 1.2) had statistical significance as prognostic factor of stage IV breast cancer patients after treatment (HR = 1.750, 95% CI 1.130-2.709, p-value = 0.012). Conclusions: After start of treatment, increased NLR can be correlated with poor cancer specific survival in stage IV breast cancer. The NLR change might be an index of response of systemic treatment.
Whole-breast hypofractionated IMRT and brachytherapy boost after conservative surgery for breast cancer: Early results of a prospective non-randomised trial.
Authors: Guix Benjamin , Garcia Ivan , Guix Ines , Lejarcegui Juan Antonio , Tello Jose Ignacio , Prats Miquel , Quinzaños Luis , Mases Joel , Algara Manel , Monne Josep Maria Sole , Guix Teresa
Published: February 2017

46

Background: To report early results obtained in a prospective group of patients (pts) treated with whole breast IMRT radiotherapy plus a brachytherapy boost to the tumor bed after conservative surgery, given either with hypofractionated or normofractionated radiotherapy. Methods: Between 12/2008 and 06/2014, 829 pts with <4cm, N0-2 breast cancers treated with conservative surgery were assigned to enter the study. Pts were offered to be treated either with IMRT hypofrationated whole breast and lymphnode areas (if needed) radiotherapy 42.6 Gy (266cGyx16 fractions) plus a 7 Gy boost to the tumor bed, (hypofractionated group) or IMRT normofractionated 50 Gy (200cGyx25) to the whole breast and lymphatic areas (when needed) plus 16 Gy brachytherapy boost (200cGyx8 fractions) (normofractionated group). Treatment assignation was done according to the patients preference or, if none, were randomly assigned to have both groups uniformly balanced. During treatment and follow-up special attention was taken to early and late side-effects, breast fibrosis, arm lymphedema, skin reaction, patient satisfaction and local, regional and distant disease control. Results: A total of 309 pts were included in the hypofractionated group and 520 in the normofractionated group. All patients completed treatment. Pts were evaluated weekly during treatment and every 3 months for the first 2 years of follow-up and in a yearly basis after. Photographs were taken at each visit. SOMA-LENT scales were used in every visit. For quality of life EORTC QLQ-C30 plus the BR-15 module were used. No pts had adverse side-effect that required treatment ending in any group. In the hypofractionated group, there were 1 LR, 1 M1 and 1 death due to the disease. In the normofractionated group there were 12 LR, 7 M1 and 4 patients died due to the disease. Conclusions: Hypofractionated IMRT to the whole breast followed by a 1 fraction HDR breast implant was a safe and effective method of treatment for early breast cancer treated with conservative surgery, even in those patients N+ in which the supraclavicular fossa was included in the treatment fields. Pts satisfaction was greater in the hypofractionated group.
Identifying patterns of breast cancer care provided at high volume hospitals: A classification and regression tree analysis.
Authors: Kong Amanda L. , Pezzin Liliana E , Nattinger Ann B
Published: February 2017

69

Background: There is a growing body of literature linking hospital volume to outcomes in breast cancer. However, the mechanism through which volume influences outcome is poorly understood. The purpose of this study was to examine the relationship between hospital volume of breast cancer cases and patterns of processes of care in a population-based cohort of Medicare patients. Methods: A previously described and validated algorithm was applied to Medicare claims for newly diagnosed breast cancer cases in 2003 to identify potential subjects. Breast cancer patients were recruited to participate in a survey study examining breast cancer outcomes, and data was merged with Medicare claims and state tumor registries. Hospital volume was divided into tertiles. A Classification and Regression Tree (CART) model was performed to look for statistically significant relationships between patterns of processes of care and hospital volume. Results: Using CART analysis, eight patterns of care were identified that differentiated breast cancer care at high versus low volume hospitals. Sentinel lymph node dissection (SLND) was the single process of care that demonstrated the greatest differentiation across hospitals with differing volumes. Four patterns of care significantly predicted that a patient was less likely to be treated at a high volume hospital. Conclusions: Our study demonstrates differences in patterns of processes of care between low and high volume hospitals. Hospital volume was associated with several patterns of care that reflect the most current standards of care, particularly SLND. Greater adoption of these patterns by low volume hospitals could improve the overall quality of care for breast cancer.
Inappropriate lumpectomy in early breast cancer: Experience from a Tertiary Care Centre in India.
Authors: Selvakumar Veda Padma Priya , Kumar Rajeev
Published: February 2017

77

Background: In India the incidence of breast cancer has shown an increasing trend over the past few decades and the majority of patients present with early breast cancer in the cities. A disturbing trend in the present setting is that a substantial proportion of patients are referred for the management of early breast cancer after inappropriate excision as diagnostic procedure in the primary care setup. Methods: The medical records of all patients who underwent surgery for early breast cancer post-lumpectomy status from September 2010 to December 2014 were reviewed retrospectively. The patterns of incision for lumpectomy, the margins of excision, the T stage, pre-operative imaging, the type of surgery and adjuvant therapy, the lapses in lumpectomy and various challenges it poses for further management and how it was combated were scrutinized in detail. Results: About one hundred and fifteen women were found eligible for the study. The mean age of onset was 47.33 years [Range 28-78]. The ratio of Left : Right were 57 : 58. The Margins and T status were known only in seventeen patients. Imaging ruled out any residual disease in breast in twenty eight patients. Twenty-seven patients underwent breast conservation with reconstruction, 82 underwent modified radical mastectomy and six of them underwent only axillary dissection. Only 41 patients had no residual primary disease on final histopathological evaluation. All patients underwent adjuvant therapy based on the approximate T staging. 12 patients were lost to follow up at one month.103 patients are alive and 101 disease free at an average follow up of 13.6 months. Conclusions: In early breast cancer, inappropriate lumpectomy for diagnostic purpose alters the course of surgical and adjuvant management. Hence it should be discouraged and not advocated as standard of care.