bluuebunny/crossref_metadata_2025 huggingface dataset:
Significance of incidentally detected oval, circumscribed enhancing lesions on preoperative breast MRI.
Authors: Lee Jong Yoon , Jang Mi Jung , Kim Sun Mi , Yun Bo La , Jang Ja Yoon
Published: February 2017

12

Background: To evaluate the characteristics and malignancy rate of oval, circumscribed enhancing lesions seen on preoperative breast MRI in patients with breast cancer. Methods: From January 2010 through May 2013, a total number of 502 oval, circumscribed mass was incidentally found in 326 patients with breast cancer who had undergone preoperative breast MRI. Seventy-eight lesions were excluded due to the lack of follow-up imaging or total mastectomy. Biopsy was performed when suspicious enhancing kinetics or interval change were detected on MRI. Otherwise, MRI or ultrasound follow up for correlated lesion were performed at least 2 years. Clinical and imaging features were recorded for analysis. Results: Of the 424 oval, circumscribed enhancing lesions detected on MRI, twelve (2.8%) were malignant and 412 (97.2%) were benign. There was no significant difference in size between malignant (0.72±0.26 cm) and benign (0.71±0.34 cm) lesions (p = 0.932). Among 424 lesions, 43 lesions (10.1%) were pathologically confirmed and twelve were malignant. Positive predictive value (PPV) of malignancy for the biopsy was 27.9%. Among 12 malignant lesions, 7 (58.3%) were invasive ductal carcinoma, 4 (33.3%) were ductal carcinoma in situ, and 1 (8.3%) was tubular carcinoma. Of the pathologically confirmed benign lesions, 8 (25.8%) were fibroadenoma, 7 (22.6%) were intraductal papilloma. Interestingly, there were significantly frequent MRI features with early fast enhancement and delayed washout pattern in malignant (11/12) compared to benign (29/412) lesions (p < 0.001). PPV of malignancy for early fast enhancement and delayed washout pattern in MRI was 27.5%. Conclusions: Cancer yield in patients with oval, circumscribed enhancing lesion on preoperative breast MRI was 12 (2.8%) of 424. MRI features with early fast enhancement and delayed washout pattern strongly suggested malignancy.
Early breast cancer response to neoadjuvant chemotherapy: Defining the optimal timing and response rate using clinical tumor measurement.
Authors: Boudreau Dominique , Santos Fabiano , Robidoux Andre , Boileau Jean-Francois
Published: February 2017

121

Background: Breast cancer pathological complete response (pCR) following neoadjuvant therapy (NAT) is associated with better survival in some tumor subtypes. There is interest in identifying methods to increase early prediction of pCR during NAT. A simple and inexpensive technique such as early clinical breast examination has been shown to correlate with pCR during NAT in some studies. However, the optimal timing of the measurement and the best tumor response (TR) rate to predict pCR still need to be defined. Methods: We conducted a retrospective cohort study of patients prospectively enrolled in the following NSABP trials in one academic center (Montreal, Canada): B-40, B-41, FB-AX-003, FB-4, FB-5 and FB-6. Patients with T4 disease or disease progression were excluded. Clinical tumor measurements were recorded before each cycle of NAT. TR was measured as the percentage decrease in the largest tumor diameter. ROC curves for TR measurements at each time point were generated, comparing areas under the curve using the DeLong method. P-value ² 0.05 was considered significant. Results: We analyzed data of 155 patients recruited from Aug. 2005 to May 2011. Results are presented in Table 1. The best time point to predict pCR was after cycle 2. At this time point, a TR of 46% was the best cutoff value to predict for pCR. Among hormone receptor positive (HR+) and HER-2 positive (HER-2+) breast cancer patients, a TR of 47% after cycle 2 was significantly predictive for pCR. These findings were similar using a 50% TR cutoff after 2 cycles. Conclusions: Observing a 50% reduction in largest tumour diameter on clinical breast examination after cycle 2 of NAT is predictive for pCR in HR+ and HER-2+ breast cancer patients. We recommend using this definition of clinical response in future trials evaluating novel methods to improve early prediction of pCR during NAT. [Table: see text]
How to reduce Ki67 variability jointly evaluating histological grade.
Authors: Izquierdo Maxim , Rodriguez Ignacio , Tresserra Fransec , Fabregas Rafael
Published: February 2017

127

Background: Proliferative tumor activity measured immunohistochemically by Ki67 has high variability. Clinical use can be improved if it is considered together with the histological grade. Methods: Ki67 value has been studied in 566 breast cancers between 2007 and 2013 at our Institution using MIBI monoclonal antibody. The histological grade and hormonal receptor status were also evaluated. Results: Histological grade was I in 293 (51.7%) tumors, II in 219 (38.7%) and III in 54 (16.8%) tumors. Estrogen receptor was positive in 166 (29.5%) tumors and progesterone receptor was positive in 95 (16.8%) tumors. None of the tumors with Ki 67 value lower than 10% had histological grade III. Only 7% of tumors with histological grade I had a Ki 67 higher than 25%. Conclusions: It has to be considered to repeat or confirm the values of Ki67 higher than 25% with histological grade I, and Ki67 values lower than 10% in tumors with histological grade III.
Distant recurrence risk with prospective use of the 21-gene assay at a single institution.
Authors: Mullinax John , Carr Danielle , Vera Nora , Sun Weihong , Lee M. Catherine , Hoover Susan , Fulp William J. , Acs Geza , Laronga Christine
Published: February 2017

131

Background: Distant recurrence (DR) is the cause of most breast cancer deaths. The 21-gene assay (ODX) Recurrence Score (RS) result predicts both 5 and 10-yr DR risk and can guide adjuvant chemotherapy (CT) recommendations to mitigate this risk. This study analyzed the use of the RS result to guide adjuvant treatment decisions in a large single-institution, prospective cohort of patients (pts). Methods: This is an IRB-approved review of a prospective database of pts receiving ODX on an initial primary breast cancer. Data collected included demographics, primary operation, margin status, receptor status, RS, adjuvant treatment, recurrence, and survival. Pts were stratified as low risk (RS < 18), intermediate risk, or high risk (RS > 30). The primary analysis computed Kaplan-Meier estimates for rate of DR at 5 yrs when pts were stratified by RS. Results: From 2003 to 2009, a RS result was obtained on 606 pts. Median follow up was 2.9 yrs (0.1-9.7) and median age was 58 yrs (27-84). Median RS result was 16 (0-63); 344(57%) pts were low, 212(35%) intermediate, 50(8%) high. Endocrine therapy was given to 92.4%, 94.3%, and 87.5% low, intermediate, and high risk pts, respectively. Adjuvant CT was given to 8.6%, 47.6%, and 70.8% low, intermediate, and high risk pts, respectively. There were 8 DR events with 1.8% 5-yr estimated risk of DR. The 5-yr estimated risk of DR was 0.7% for low risk (344) pts, 3.4% for intermediate risk (211) pts, and 2.6% for high risk (50) pts. Among node negative [N(-)] pts (502), the 5-yr estimated risk of DR was 0.8% for low risk (287) pts, 3.7% for intermediate risk (174) pts, and 3.3% for high risk (41) pts. Among node positive [(N+)] pts (54) there was only 1 DR, which was in a high risk pt. Of pts with unknown nodal status (50), there were no DRs. Conclusions: The RS result is predictive of DR at 5 yrs as shown in historical datasets (Table). The use of ODX to guide adjuvant treatment recommendations in our contemporary, prospective cohort resulted in a much lower 5-year DR rate and thus supports its use to guide adjuvant treatment decisions. [Table: see text]
Racial/ethnic disparities in HER2-positive breast cancer in the era of adjuvant trastuzmab.
Authors: Caggiano Vincent , Parise Carol
Published: February 2017

139

Background: Racial/ethnic disparities in breast cancer survival have been well-documented. Trastuzumab was FDA approved for adjuvant treatment of HER2-positive breast cancer in November, 2006 and has improved survival in these patients. The purpose of this study is to determine if racial disparities have changed in patients who were diagnosed with HER2 positive breast cancer in 2007-2012 when compared with patients who were diagnosed in 2000-2006. Methods: Using the California Cancer Registry, we identified 32,597 cases of first primary female invasive HER2-postive breast cancer. Cases were divided into two cohorts: Early - diagnosed in 2000-2006; Late - diagnosed in 2007-2012. Kaplan-Meier 6-year survival and Cox regression analysis was conducted to assess risk of mortality of African Americans, Hispanics, Asian/Pacific Islanders, and American Indians when compared with whites. Analyses were conducted separately for each cohort and adjusted for stage at diagnosis, grade, age, and socioeconomic status. Hazard ratios and 95% confidence intervals were reported. Use of trastuzumab was not documented. Results: When combining all HER2-positive subtypes (ER+/PR+/HER2+, ER-/PR+/HER2+, ER+/PR-/HER2+, ER-/PR-/HER2+), blacks had an increased risk of mortality (HR = 1.32; 95% CI: 1.16-1.49), in the early cohort but there were no differences for any other race. There were no differences in mortality by race/ethnicity in the late cohort. Separation of the HER2-positive subtypes showed that African Americans with the ER+/PR+/HER2+ subtype had higher mortality than whites (HR = 1.43; 95% CI: 1.17-1.75) in the early cohort but there was no difference in the late cohort. There were no racial disparities within either of the cohorts for the ER-/PR-/HER2+ subtype. Conclusions: Although we were unable to document use of anti-HER2 treatment, the era of adjuvant trastuzumab appears to have attenuated the black/white disparity in HER2 positive breast cancer.
Early detection of mammary tumors in vivo using a highly specific tumor antibody.
Authors: Dréau Didier , Moore Laura Jeffords , Das Roy Lopamudra , Wu Shu-ta , Puri Rahul , Mukherjee Pinku
Published: February 2017

14

Background: Earlier detection of abnormal cells using target-specific techniques holds great promise. One of those targets Mucin-1 (MUC1) is expressed as a hypo-glycosylated form (i.e., tMUC1) in 95% of breast tumors and plays a crucial role in cancer progression. We have developed Tab004, a monoclonal antibody highly specific to a protein sequence accessible in tMUC1. Here we present data assessing the specificity and sensitivity of Tab004 in vitro and in genetically engineered mice in vivo overtime. Methods: We have developed human MUC1 Tg mice that were bred to mice that carry the oncogene, polyoma middle T antigen driven by the MMTV promoter. These mice designated MMT develop mammary gland tumors spontaneously and expresses the human form of tMUC1. PyVMT and C57Bl/6 served as controls. Mice develop mammary gland hyperplasia between 8-10 weeks of age that progresses to ductal carcinoma in situ by 12-14 weeks and adenocarcinoma by 18-24 weeks. Approximately 40% of the mice develop metastasis to the lung and other organs. The tumor progression appropriately mimics the human disease. MMT mice (n = 20) were injected twice monthly retro-orbitally with 12.5ug (100uL) of Tab004-conjugated to indocyanine green (ICG) and imaged thereafter from 8 to 22 weeks of age. Fluorescence was assessed 4 and 24 hrs post injection using the IVIS system. At euthanasia, tissue was collected for further analyses. Further, human breast tumor and normal mammary epithelial tissues were evaluated by immunohistochemical staining. Results: Tab004 specifically recognizes tMUC1 and not normal MUC1. In MMT mice, ICG-conjugated Tab004 allowed early detection of tumors in vivo sparing recognition of normal mammary epithelia in the C57BL/6 mice or in the PyV MT tumors. Detection with ICG-conjugated Tab004 allowed monitoring of tumor progression overtime. Importantly, ICG-conjugated Tab004 permitted significantly earlier detection than physical examination. Conclusions: The data highlight the specificity and the sensitivity of Tab004 in detecting tMUC1 in vitro, in situ and in relevant murine models in vivo. Thus, Tab004 will have significant clinical relevance for development as a targeted imaging agent and in the future for targeted drug delivery.
Investigation of potential salivary biomarkers for the diagnosis of breast cancer.
Authors: Jinno Hiromitsu , Murata Takeshi , Sunamura Makoto , Sugimoto Masahiro
Published: February 2017

145

Background: Saliva is an easily accessible and informative biological fluid which has high potential for the early diagnosis of diseases. Saliva-based diagnostics, particularly those based on metabolomics technology, offer a promising clinical strategy by characterizing the association between salivary analysts and a particular disease. The aim of this study is to investigate potential biomarkers in human saliva to facilitate the early diagnosis of breast cancer. Methods: We conducted a comprehensive metabolite analysis of saliva samples obtained from 60 breast cancer patients and 20 healthy controls, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). Statistical analyses were performed by using a nonparametric Mann-Whitney U test, multiple logistic regression and the receiver operating characteristics (ROC) to evaluate the predictive power of biomarkers. Results: Forty-nine patients (81.7 %) had invasive ductal carcinoma (IDC) and 9 patients (15.0 %) had ductal carcinoma in situ. In 33 patients receiving neoadjuvant treatment, saliva samples were obtained just before surgery. After removing the concomitantly observed peaks and noise peaks, an average of 205 peaks were derived from the metabolites. Among these peaks, five potential salivary biomarkers demonstrated significantly higher concentrations in breast cancer patients comparing with healthy individuals (p < 0.05). Especially, salivary biomarkers obtained from patients with IDC before neoadjuvant treatments tended to be higher concentrations than those obtained after treatment. In these metabolites, the area under the ROC curves (AUCs) were 0.765 for substance A, 0.716 for substance B, 0.809 for substance C, 0.819 for substance D and 0.850 for substance E. Conclusions: Salivary metabolites are promising biomarkers for the early diagnosis of breast cancer.
Elevated neutrophil to lymphocyte ratio to predict survival outcome after recurrence for patients with triple-negative breast cancer.
Authors: Iwase Toshiaki , Sangai Takafumi , Sakakibara Masahiro , Nagashima Takeshi , Miyazaki Masaru
Published: February 2017

24

Background: Recent studies show that obesity plays a major role in causing chronic inflammation by producing several inflammatory cytokines. On the other hand, there is limited research focusing on the effect of obesity in recurrent breast cancer treatments. Therefore, we set out to clarify the impact of obesity related inflammation by Neutrophil to Lymphocyte ratio (N/L ratio) in recurrent breast cancer treatment. Methods: From January 2005 to December 2014, 93 patients with recurrent breast cancer after surgery were included. World Health Organization body mass index (BMI) classification was used for evaluating the degree of obesity. Muscle mass amount was also analyzed. Lumber skeletal muscle index (LSMI, cm2/m2) was generated by standardizing each patient’s muscle area (m2) at the third lumber vertebrae level in axial CT data. Less than 50m2 in LSMI was defined as pre-sarcopenia. N/L ratio was calculated from the laboratory data, and more than 3.0 was defined as high N/L group. Results: Patient background showed there were 20 overweight patients and 2 obese patients. Twenty-eight cases had pre-sarcopenia. In univariate analysis, N/L ratio had no significant differences among BMI categories. However, triple negative (TN) type demonstrated significantly high N/L ratio compared to other subtypes (p < 0.05). LMSI had significant negative correlation to N/L ratio (p < 0.05). In survival analysis, Overweight/Obese group showed significantly shorter OS (p < 0.05). High N/L ratio group also showed similar results (p < 0.05). When stratified by intrinsic subtypes, TN type demonstrated significantly shorter OS (p < 0.05). Additionally, Overweight/Obese groups in TN type had notably shorter OS (p < 0.05). In multivariate analysis, subtype and N/L ratio were independently related to OS (Hazard ratio: 3.3 in TN type, 2.9 in High NL ratio group). Conclusions: Present study did not show any significant relationship between obesity and chronic inflammation in recurrent breast cancer setting. On the contrary, intrinsic subtype was significantly related to inflammation, leading to pre-sarcopenia and worse OS. Whether obesity promotes inflammation in TN type needs more investigation.
Human insulin to increase breast cancer risk in Taiwanese women with type 2 diabetes.
Authors: Tseng Chin-Hsiao
Published: February 2017

26

Background: To investigate whether human insulin use may be associated with risk of breast cancer in Taiwanese women with type 2 diabetes. Methods: The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 482,065 women with type 2 diabetes were followed up for breast cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, cumulative dose and cumulative duration of insulin) were calculated and the multivariable-adjusted hazard ratios were estimated by Cox regression. Results: There were 59,830 ever-users and 422,235 never-users, with respective numbers of incident breast cancer of 559 (0.93%) and 4,711 (1.12%), and respective incidence of 207.7 and 215.1 per 100,000 person-years. The overall adjusted hazard ratios (95% confidence intervals) did not show a significant association with insulin [1.098 (0.994-1.212)]. However, significant trends for the different categories of the dose-responsive parameters were observed. Patients in the third tertiles consistently showed a significantly higher risk of breast cancer while compared to never-users: 1.263 (1.093-1.458), 1.339 (1.164-1.540) and 1.331 (1.158-1.531) for ≥ 67 months for time since starting insulin, ≥ 39,000 units for cumulative dose of insulin, and ≥ 21.8 months for cumulative duration of insulin, respectively. Conclusions: This study discloses a significantly higher risk of breast cancer associated with the use of human insulin, demonstrating a significant dose-responsive relationship.
Age-related variations: A retrospective analysis of 851 prospectively collected patient samples to determine the benefit of combining combinatorial protein biomarker assay for risk assessment in women with dense breast.
Authors: Reese David Emery , Silver Michael , Henderson Meredith C. , Borman Sherri , Corn Christa , Mulpuri Rao , Benson Kasey
Published: February 2017

27

Background: Clinicians often experience difficulty in differentiating benign lesions from invasive breast cancers in patients designated as dense breast. A major limitation of radiological breast cancer screening methods involves a decrease in sensitivity and specificity in women with dense breast. Thus, we sought to test whether Klarify Breast, a combinatorial protein-based biomarker panel could improve early detection of significant breast lesions in a controlled fashion. Clearly, a diagnostic assay that would provide biochemical evidence in the patient’s clinical course is greatly needed. Methods: We have conducted two independent, multi-center, prospective clinical trials to establish the clinical validity of Klarify Breast – an assay that uses multiple Serum Protein Biomarkers (SPBs), Tumor-Associated Autoantibodies (TAAbs), patient specific clinical data and develop a score to differentiate patients with benign breast disease from those with invasive breast cancer. Independent panels of biomarkers and associated algorithms were developed using prospectively collected samples from women under age 50 (n = 351) and from women ages 25-75 (n = 500). Here, we present the benefit of integrating the results of Klarify Breast test with patient imaging to best assess risk in women with dense breast. Results: While performance of the assay was somewhat age dependent (women under the age of 50 demonstrated a higher sensitivity and specificity than women over the age of 50). Here we present data that both groups of women clearly benefit from the addition of a biomarker assay combined with standard of care imaging in identifying invasive breast lesions. Conclusions: Clearly, in women with dense breast, where radiologic studies alone do not permit full assessment in women with a dense breast finding. The biomarker test here, comprised of TAAbs and SPBs, offers a clear advantage in terms of NPV, PPV, Sensitivity and specificity. The results argue strongly for the use of appropriate biomarkers to augment imaging based breast cancer screening in women with dense breast or those who are at high risk. Clinical trial information: NCT01839045, NCT02078570.
Concordance of preoperative US-guided tattooing of axillary lymph nodes to sentinel lymph nodes and comparison of their pathologic results according to imaging modalities in breast cancer patients.
Authors: Kim Hye Jung , Jung Jin Hyang , Park Ho Yong , Park Ji-young
Published: February 2017

28

Background: We wanted to know the concordance of preoperative ultrasound (US)-guided tattooing of axillary lymph nodes (ALNs) to sentinel lymph node and to correlate MR and PET-CT findings with the final histologic results. Methods: Axillary US examination was performed for all breast cancer patients before sentinel lymph node biopsy. The detected lymph nodes in US were classified as negative (group I, enlarged but image-benign) or positive (group II, image-suspicious) finding for metastases based on US, MRI and PET-CT findings. US-guided tattooing for ALNs was performed preoperatively by injection of 3cc of activated charcoal into the cortex of lymph node and the adjacent soft tissue. We evaluated their concordance to sentinel lymph node and correlated the histologic results of US tattooed LN according to each imaging modality. Results: Forty ALNs were tattooed and sentinel nodes corresponded to tattooed nodes in all except one patient with a tattooed non-sentinel node. Ten in group I and 30 in group II on US, 18 in group I and 22 in group II on MR, and 19 in group I and 21 in group II on PET-CT. Eight cases had evidence of metastases in final histology, 2 (20.0%) in group I and 6 (20.0%) in group II on US, 4 (22.2%) in group I and 4 (18.1%) in group II on MR, and 6 (31.6%) in group I and 2 ( 9.5%) in group II on PET-CT. Conclusions: US-guided tattooing is a feasible method for marking ALNs. In addition, tattooed lymph nodes correlate well with sentinel nodes, which may obviate the need for additional localization for axillary staging.
Group visits for women at high risk for breast cancer: Facilitated education and support sessions.
Authors: Trotter Kathryn , Seewaldt Victoria , Riley Stephanie
Published: February 2017

30

Background: Women at increased risk for breast cancer frequently have anxiety and stress. They often have questions and concerns that are not discussed at their medical appointment. Methods: The Duke High-Risk Breast Clinic consists of over 1,110 women undergoing high-risk screening due to 1) BRCA-mutation, 2) familial pattern of breast cancer inheritance, 3) prior abnormal biopsy, or 4) > 20% lifetime risk of breast cancer. Approximately 31% of clinic participants are African-American and 65% are European-American. Women participating in the Duke High-Risk Breast Clinic were offered a monthly, hour-long education and support session at no charge. The goal was to help women answer key questions and provide a supportive environment. A five-month pilot was initiated in 02/2015. The NP adapted the Centering Healthcare Institute’s group visit model (www.centeringhealthcare.org). Attendees completed a Self-Assessment Sheet (SAS) on arrival. A clinic conference room was used, with chairs arranged in a circle, and refreshments available. After an icebreaker opening, the NP led a facilitated discussion on timely topics, which the patients actively prioritized. Guest experts (radiologist, geneticist, gynecologist, mental health provider) also participated. A participant or the team navigator led the closing activity, and then a brief patient satisfaction survey was completed. Patient support persons were welcomed. Results: 100% of the participants (N = 38) strongly agreed that the educational session was a resourceful way of addressing healthcare concerns, and 92% agreed that they would attend more educational sessions. Several women came at least 3 of the sessions with 30% traveling 1-3 hours. Comments were positive. Common topics on the SAS were: genetic risk/testing, risk factors for breast cancer, screening tests/tools, and nutrition. Further topics requested: “When to be concerned about aches, pains, ‘lumps’, and how not to over react”, research updates, 3D imaging, and stress. Conclusions: Women found this group visit model highly informative and helpful. Several commented they would like the sessions to be longer, or be offered in the evening. Further commitment to this group visit format is warranted.
Implantable marker to facilitate use of hypofractionated radiation in early breast cancer.
Authors: Cross Michael , Ross Joe , Jones Scott , Smith Arnold , Beck Thadeus
Published: February 2017

38

Background: Shorter courses of radiation therapy have advantages for patients and could result in significant cost savings for the healthcare system. The British and Canadian experience with hypo-fractionated regimens have shown that survival rates in appropriately selected patients is equivalent to other methods. However, adoption of these techniques has been hindered by fear of potential complications such as poor cosmetic outcomes. By improving targeting of the surgical tumor bed, an increased use of "field in field" planning helps to decrease "hot spots" commonly related to toxicities. This could potentially assist with increased use of hypo-fractionated regimens in a reliable, safe and cost-effective manner. To determine the ability of a new surgical implant marker to facilitate use of hypofractionated radiation delivery, we prospectively studied the radiation regimens delivered to 100 patients implanted with the device in our community-based practice. Methods: Over a 36 month period, 110 volumetric tissue markers were surgically implanted at the tumor bed excision site in 109 patients during partial mastectomy (PM). Routine CT imaging of the breast was performed for treatment planning and the marker was rated for visibility and its utility in delineating the target region. Radiation treatment regimens were recorded and reported. A cost analysis was also performed. Results: In all patients, the marker was easily visible and in 95.7% of cases, it was found to be useful during radiation treatment planning for RT target delineation. 36.8% of patients received conventional full-course whole breast irradiation plus boost, 56.6% received hypo-fractionation plus boost, and 4.3% received accelerated partial breast irradiation. With routine use of the implant, there was a marked increase in the use of hypo-fractionated regimens, resulting in a 25% cost savings per patient. Conclusions: This 3-dimensional implant was easily visible and particularly useful in targeting the tumor bed when implanted during PM. With routine use of the device we observed an unanticipated increased use of accelerated radiation protocols, a net cost savings in patients' treatment and a significant improvement in cosmetic outcomes.
Impact of margin status and re-excision on local control in patients undergoing breast-conservation therapy for ductal carcinoma in situ.
Authors: Shaikh Talha , Li Tianyu , Sheikh Fatima , Murphy Colin T. , Zaorsky Nicholas , Bleicher Richard J. , Sigurdson Elin R. , Goldstein Lori J. , Hayes Shelly B , Anderson Penny R
Published: February 2017

57

Background: The purpose of this study was to identify the impact of final surgical margin (SM) status, SM width, and re-excision on outcomes in patients with ductal carcinoma in situ (DCIS) undergoing breast conservation therapy (BCT). Methods: The study population consisted of women diagnosed with DCIS undergoing BCT between 1989-2014. All women received adjuvant whole breast radiation plus a boost. The primary endpoint was local control (LC) defined as an ipsilateral breast failure. A negative SM was defined as > 2 mm, close SM was defined as > 0 to < 2 mm, and a positive SM was defined as tumor at the inked SM. Cox proportional hazards model was used to determine predictors of outcomes on multivariate analysis (MVA). Actuarial incidence of LC was estimated using the Kaplan-Meier method. Results: A total of 498 patients were included. The median age was 58 (range 30-91) and the median follow-up was 8.3 years (3 months-27 years). A total of 400 patients had a final negative SM, 87 had a close SM, and 11 had a positive SM. A total of 172 patients received adjuvant hormonal therapy, 265 patients required at least one re-excision. Patients with positive or close SMs were more likely to receive a radiation dose > 60 Gy (p < 0.001) and undergo re-excision (p < 0.01). The 10-year LC rates were not significantly different between patients with a negative (93.5%), close (91.8%), or positive (100%) SM (p = 0.57). There was no difference in 10-year LC rates according to a SM width of 0-1 mm (100%), > 1 to 2 mm (88.5%), or > 2 mm (93.5%) (p = 0.85). On univariate analysis, there was no significant difference in LC when comparing negative versus close or positive (p = 1.0) SMs. There was no difference in LC in patients undergoing re-excision for initial close or positive SMs (p = 0.55). On MVA, after controlling for age, dose, hormonal therapy, comedo subtype, and grade, there were no factors associated with LC. Conclusions: This large single-institution experience demonstrates that risks of local failure remain poorly characterized. Re-excision and whole breast radiation plus boost resulted in excellent LC for women with DCIS. Our data suggests that trials aimed at personalized de-intensified local therapy are warranted.
Rapid intraoperative digital specimen tomosynthesis.
Authors: Kaufman Cary Steven , Behrndt Valerie , Hill Laurie , Caro Rebecca , Nix Sid , Zacharias Karen , Evans Erik , Mahon Carol , Ness Karen , Schnell Nancy
Published: February 2017

59

Background: About 75% of newly diagnosed breast cancers are not palpable and require image localization to remove the target lesion. Digital specimen mammography devices were developed to identify lumpectomy targets in the operating room. Despite the availability of two-dimensional digital specimen mammography (2D), the re-excision rate for lumpectomy remains significant. Specimen tomosynthesis (3D) may provide a more detailed image than standard 2D with consecutive image slices of the lumpectomy specimens for immediate review. Methods: A consecutive series of 28 breast cancer patients underwent intraoperative specimen imaging with both 2D and 3D imaging. Data recorded for each specimen on each device included 1) accuracy of identification of target lesion, 2) time required to produce comparable images, 3) ease of forwarding images via PACS to radiology, 4) predicted closest margin according to each specimen imaging device compared with final pathologic measured margin, and 5) ease of use by the surgeon and/or nurse. Results: The central focus of all 28 lesions were accurately identified with both 2D and 3D. After a short learning curve, details on the tomosynthesis images were seen not clearly shown on the 2D unit including some spiculated masses and architectural distortions. The location of closest margin was more specific with the 3D device due to “Z-axis” measurements which obtain the vertical distance of the target within the specimen. The spatial relationship of marginal calcifications or marking clips at the edge of the specimen provided by the 3D “Z-axis” was superior to the 2D orthogonal views. Although the time taken to obtain the 3D image was 74 seconds longer than a single image with the 2D device (106 vs. 32 seconds), this was equal to the time taken to obtain the two orthogonal images using the 2D device. Ease of use was equal for both 2D and 3D. Too few patients with positive margins were found to assess a difference in intraoperative positive margin prediction. Conclusions: Our initial experience with 3D tomosynthesis of lumpectomy specimens demonstrate clear images and increased information available for the breast surgeon. Research is planned to further examine the added value of high resolution tomosynthesis in breast surgery.
Two-year outcomes of a prospective study of proton therapy for breast cancer regional nodal irradiation.
Authors: Bradley Julie Ann , Dagan Roi , Ho Meng Wei , Rutenberg Michael Scott , Li Zuofeng , Mendenhall Nancy P.
Published: February 2017

65

Background: Through improved nodal coverage and decreased dose to the heart and lung, proton therapy (PT) may improve the therapeutic ratio for treatment of breast cancer requiring regional nodal irradiation (RNI). The purpose of this study is to report 2-year disease control and toxicity. Methods: From May 2012 to February 2014, 18 women (stage IIA-IIIB) were prospectively enrolled on a pilot study. Median age was 51.8 yrs (range, 42-73), with equal division between breast-conserving therapy (BCT) and mastectomy and right- and left-sided cancers. Median number of positive nodes among the 16 node-positive patients was 2 (range, 1-14). Five patients had ≥ 10 nodes positive on axillary dissection (N3a). Treatment targets (clinical target volumes for breast/chest wall, supraclavicular, axillary, internal mammary nodes) and organs at risk were delineated on CT scans. PT alone was used for 10 patients (9 postmastectomy; 1 postBCT) and combined proton-photon in 8 (all BCT). Toxicity was prospectively recorded using CTCAE v4.0. Results: Median follow-up was 1.9 yrs (range, 0.3 – 1.7). Two-year overall survival was 94% and locoregional control was 100%. Two-year distant metastases-free survival was 76%. No grade 4+ toxicity developed. Two patients developed grade 3 cellulitis. One patient had a reconstructive failure associated with postsurgical cellulitis. A right-sided patient was diagnosed with congestive heart failure 2 months after completing PT after diagnosis of a pulmonary embolus 1 month prior. She had elevated B-type natriuretic peptide before PT after adriamycin-based chemotherapy. Mean heart dose was 0 Gy and cardiac V5 0%. Grade 2 toxicities included pneumonitis in 1 patient who received concurrent chemotherapy, fatigue (n = 1), breast atrophy after removal of a 10x6x3cm lumpectomy cavity (n = 1), and lymphedema in 1 patient with > 20 nodes surgically excised. One patient with a history of rib fractures developed an ipsilateral rib fracture 7 months after PT. Conclusions: For women with locally advanced breast cancer, PT for RNI has proven feasible after either mastectomy or BCT. PT allows for highly conformal radiation delivery without compromise of target coverage or excess exposure of normal tissue. Clinical trial information: NCT01365845.
Impact of primary care providers on patient screening mammography and initial presentation in an underserved clinical setting.
Authors: Keshinro Ajaratu , Hatzaras Ioannis , Dhage Shubhada , Rifkind Kenneth , Joseph Kathie-Ann P.
Published: February 2017

8

Background: Screening mammography (SM) is a routinely used modality for earlier detection of breast cancer and is effective in reducing breast cancer-related morbidity and mortality. A better understanding of the impact of access to primary care physician (PCP), on the screening protocols and stage presentation, is needed to address the issue of breast cancer stage disparity amongst underserved women. Methods: A retrospective chart review of the electronic medical record, for breast cancer patients newly diagnosed from 2012-2013, was performed using the tumor registry at Bellevue Hospital Center, the largest public hospital in New York City. Patients with recurrent breast cancer, stage IV breast cancer, and those that weren’t managed surgically at our institution, were excluded from the study. Data including patient demographics, established relationship with PCP, and screening mammogram and palpable mass at presentation, were obtained and analyzed using SPSS Statistics Software. Results: 173 patients were included in the study of which 5 presented with bilateral breast cancer (n = 178). The majority of the patients seen at our institution were from minority groups, primarily Hispanic (34%) and Chinese (23%). 129 patients (72%) had a PCP at the time of diagnosis versus 49 patients (28%) without a PCP. Patients without a PCP were more likely to have a palpable breast mass at presentation, compared to patients with a PCP (73% vs. 42% respectively, p < 0.05). Furthermore, only 32 % of patients without a PCP had a SM at time of presentation, compared to 61% of patients with a PCP (p = 0.003). Overall, in the group of patients with a PCP, the majority presented with stage I breast cancer (43%), followed by 29% with stage 0. In comparison, the majority of patient without a PCP presented with stage II (41%), followed by 29% with stage I (p = 0.019). Conclusions: There is a benefit for patients with access to a PCP, as it leads to a higher likelihood of breast cancer detection via SM, as opposed to a symptomatic presentation, such as a palpable mass. Therefore, these patients are more likely to be diagnosed with an earlier stage of breast cancer, which improves their mortality.
Impact of comorbidities on surgical outcomes following mastectomy in elderly breast cancer patients: An analysis of the NSQIP database.
Authors: Mays Simone , Moo Tracy-Ann , Simmons Rache M.
Published: February 2017

88

Background: Approximately 4% of women age 70 will develop breast cancer during the next ten years. There is limited data on surgical outcomes in elderly patients undergoing treatment for breast cancer. This study examines complications following mastectomy in elderly patients and determines how comorbidities impact those outcomes. Methods: The American College of Surgeons National Surgery Quality Improvement Program database was used to examine complications and comorbidities in breast cancer patients 70 or older undergoing mastectomy from 2007-2012. The relationship between complication and comorbidity was characterized using descriptive statistics and Wilcoxon rank-sum test. Variable frequencies were compared using Chi-square or Fisher’s exact test with a statistically significant two-sided p-value set at 0.05. Results: We identified 12,026 patients 70 or older who underwent mastectomy. The 30-day overall morbidity rate was 4.22%. Myocardial infarction (MI) was associated with history of bleeding disorder and cerebral vascular accident (CVA) (P < 0.05). Prior CVA, transient ischemic attack and MI were associated with post-operative CVA (p < 0.05). Chronic obstructive pulmonary disease and steroid use impacted post-operative pneumonia (p < 0.05). Bleeding disorder, hypertension, and steroid use impacted urinary tract infection occurrence (p < 0.05). Diabetes increased the rate of wound dehiscence (p = 0.001). Conclusions: The 30-day morbidity rate of elderly breast cancer patients undergoing mastectomy is low. Although the complication rate is low, certain comorbidities increase the risk of specific complications. Appropriate measures should be taken to optimize comorbidities in elderly patients to further minimize adverse outcomes.
A new method for partial breast reconstruction: 3-year New Zealand experience.
Authors: Govender Stan , Harman John , Lebovic Gail , Simpson John , Benjamin Benji
Published: February 2017

89

Background: Most women in New Zealand undergo partial mastectomy (PM) and 6 weeks of whole breast irradiation for early breast cancer. Oncoplastic surgery (OPS) is common, however, reconstruction of the breast during partial mastectomy presents challenges for radiation targeting since tissues have been extensively rearranged. Further complicating matters, the seroma cavity is often absent, and many patients travel to different cities for radiation without much communication between the surgeon and radiation oncologist prior to treatment. Throughout the country there is interest in promoting hypofractionated or accelerated radiotherapy, however, these techniques cannot be popularized without accurate targeting to minimize complications. In this series of patients we studied a new method of breast reconstruction using a bioabsorbable implant that serves as a surgical site marker as well. Methods: Following informed consent, 15 women were studied in a prospective manner. The bioabsorbable implant was sutured into the tumor resection site, and tissue flaps were directly attached. Radiation treatment protocols followed ASTRO guidelines. Results: The implant provided volume replacement and acted as a scaffolding for the breast tissue flaps providing local reconstruction. Cosmetic outcomes were excellent in all patients, no device related or radiation complications occurred. One patient had a post-operative hematoma that resolved without intervention, there were no post-operative infections. 3 year follow up shows no tumor recurrences, and no untoward effects. When compared to conventional radiation targeting, use of the implant showed a > 50% reduction in treatment volume is possible. 3 year mammograms show normal regrowth of tissue without artifact and with minimal fibrosis. Conclusions: Three year follow-up shows this "mini" breast implant assists with oncoplastic breast reconstruction, while at the same time clearly marks the surgical site of tumor excision. Patients tolerated it well, and radiotherapy planning, positioning and treatment were all facilitated by the implant. Excellent patient outcomes in this pilot study have resulted in a national evaluation of this method in the public healthcare sector.
Health-related quality of life of of women with breast cancer undergoing chemotherapy in the northern region of Brazil.
Authors: Sawada Namie Okino , Santana Mary Elizabeth de , Sonobe Helena Megumi
Published: February 2017

92

Background: In Brazil, the estimate for the year 2015 is approximately 576,000 new cases of cancer. Breast cancer is the most common in Brazilian women and the state of Pará is the first with the highest incidence of breast cancer in northern Brazil. The high incidence and changes caused by treatment and own illness as the disturbances in body image, functional, emotional and social changes cause fear in women, as well as disrupting daily activities and impact the health-Related Quality of Life (HRQOL). Improving HRQOL is an important goal so the evaluation of HRQoL of these patients is of interest to health professionals, as they provide information that help in planning treatment and rehabilitation. The objective is to evaluate the HRQoL of patients with breast cancer in chemotherapy treatment. Methods: It is a cross-sectional study with quantitative exploratory design. This place was a public hospital in the city of Belém do Pará, Women were included with breast cancer, over eighteen years old and excluded those with cognitive problems and metastases. The European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ C 30) and Questionnaire Breast Cancer Module (QLQ BR23) have been administrated. The project was approved by the Ethics Committee and were respected the resolution 466/2012 CNS / MS. Results: The sample consisted of 89 women with breast cancer undergoing chemotherapy, most in the age group over 40, mulatto, married, fundamental level of education, domestic load, Catholic religion, live in rural areas with incomes of one to two minimum salaries. The EORTC QLQ C 30 showed that the average QOL was 75.56, and the most impaired functions were physical (M = 65.62) and role performance (M = 58.61) and the most frequent symptoms were diarrhea, constipation, dyspnea, nausea and vomiting, fatigue, pain and loss of appetite. EORTC BR23 demonstrated functional scale (M = 49.95) and symptoms scale (M = 33.00). Conclusions: The results show that the side effects of chemotherapy affect the physical and functional function and consequently HRQoL of these patients.
Factors influencing fatigue in breast cancer patients undergoing breast irradiation.
Authors: Perry Edward Belk , Mulay Sudhanshu Bharat , Kamath Jayesh , Dowsett Robert J. , Neuwirth Jacob , Grady James , Gold Courtney , Liang Bruce , Tannenbaum Susan
Published: February 2017

96

Background: We are conducting an exploratory, prospective study to investigate factors associated with radiation-induced fatigue in women with early breast cancer undergoing radiation therapy (RT) for breast conservation. Our hypothesis is that fatigue associated with adjuvant RT is related to tissue damage by apoptosis and inflammation, and to baseline psychological profiles. Methods: All subjects were assessed immediately before RT (T1), mid-point of RT (T2), end of RT (T3), 6 months (T4) and 1 year (T5) after completing RT. Clinical evaluations of skin toxicity, laboratory measures, fatigue, distress, depression, anxiety, sleep, energy and pain were assessed using validated measures. Results: Thirty-one subjects (target 50) have been enrolled to date; 23 have completed T3 and are presented here. 35% had a history of depression and 17% are currently depressed; 22% had past and current anxiety. BCTOS breast pain, tenderness and sensitivity increased during RT and were consistent with functional pain scores. No clinically relevant changes in energy or distress were seen. Despite a notable prevalence of depression and anxiety at baseline, there were no relevant changes in depression or anxiety. Most IL-1β, IL-4, IL-6 and IL-10 levels were undetectable. 39% of subjects showed increases in fatigue and were 14 years younger than non-fatigued subjects. Fatigued subjects had more frequent past (44%) and current (33%) depression than non-fatigued subjects (29% and 7%, respectively), and woke up tired more frequently (44% versus 0%). Current depression, but not fatigue, was associated with decreased a.m. cortisol levels during RT. 56% of fatigued subjects had an RTOG Acute Skin Toxicity score > 1 and 78% had BCTOS breast-specific pain subscales scores ≥ 3 during RT vs. 21% and 14% of non-fatigued subjects, respectively. Serum caspase-1 (inflammation) and caspase-3 (apoptosis), hs-CRP and TNF-α were increased but not associated with fatigue. Conclusions: Our preliminary findings suggest that radiation-associated fatigue is complex and, as hypothesized, is dependent on a patient’s psychological profile in the setting of skin toxicity and insomnia. If this data holds at study completion, it may guide clinical interventions.