bluuebunny/crossref_metadata_2025 huggingface dataset:
Weekly nab-paclitaxel followed by FEC in patients with operable breast cancer: Phase II study.
Authors: Seki Hirohito , Asamuna Fumiki , Morinaga Shyoujiro , Suzuki Keiichi , Kaneda Munehisa , Kamiya Noriki , Ishii Yoshiyuki , Osaku Masayoshi , Ikeda Tadashi
Published: February 2017

138

Background: Nanoparticle albumin-bound paclitaxel (nab-PTX) has a high transitivity into tumor tissue compared to solvent-based paclitaxel (sb-PTX). In a phase III study in patients with metastatic breast cancer, nab–PTX demonstrated nearly double the response rate and significantly longer time to tumor progression than paclitaxel. However, the current problems are that nab-PTX is a higher rate of discontinuation and sensory neuropathy than sb-PTX. We sought to evaluate the efficacy and safety of nab-PTX followed by FEC. Methods: In this study, patients were received 4 cycles of nab-PTX (80 mg/m2) q1w (days 1, 8, and 15 of each 4-week cycle) followed by 4 cycles of FEC q3w. The primary endpoint was pCR rate (ypT0/is ypN0). The secondary endpoints included clinical response rate, disease-free survival, breast-conserving surgery rate, and safety. Results: Forty patients were enrolled; the median age was 53 (range 33-81), postmenopausal women were 62.5%. ER positivity, PgR positivity and HER2 positivity were 62.5%, 52.5% and 37.5%, respectively. Clinical stage for I, II and III were 30%, 62.5% and 7.5%, respectively. The pCR rate (ypT0/is ypN0) was 40% (16/40). In the subtype subset, pCR rates were Luminal A 20% (1/5), Luminal B (HER2 negative) 15.4% (2/13), Luminal B (HER2 positive) 60% (6/10), HER2 enrich 80% (4/5) and TNBC 42.9% (3/7). The breast-conserving surgery rate was 77.5% (31/40). The clinical response rates were cCR 20.0% (8/40), cPR 52.5% (21/40), cSD 25% (10/40) and cPD 2.5% (1/40) after 4 cycles of nab-PTX, cCR 32.5% (13/40), cPR 42.5% (17/40), cSD 20% (8/40) and cPD 5% (2/40) after nab-PTX followed by FEC. Ninety-eight percent patients completed 4 cycles of planned protocol dose of nab-PTX and 62.5% completed FEC. The Grade3/4 hematologic toxicity of nab-PTX was only neutropenia 2.5%. Grade1/2 non-hematologic toxicity were neuropathy 12.5%, arthralgia 7.5% and myalgia 7.5%. Grade3/4 non-hematologic toxicity was no reported. Conclusions: This is the first study to evaluate weekly nab-PTX (80 mg/m2) followed by FEC for operable breast cancer. Our results demonstrated that weekly nab-PTX (80 mg/m2) followed by FEC was well-tolerated and resulted in increased pCR rate than reported data of nab-PTX. Clinical trial information: UMIN000011048.
Tumor subtype and race in male breast cancer: A population-based cohort study.
Authors: Aydogan Fatih , Sagara Yasuaki , Mallory Melissa Anne , Tukenmez Mustafa , Golshan Mehra
Published: February 2017

149

Background: Subtypes of female breast cancer have been shown to vary by race, however data on the significance of molecular profiling and the distribution of subtype according to race/ethnicity for male breast cancer is lacking and warrants research. We sought to investigate the differences in male breast cancer according to tumor subtypes and racial/ethnic profiles using the Surveillance, Epidemiology, and End Results Program (SEER) database. Methods: We used the SEER database (SEER 18 registries) to identify all cases of male breast cancer diagnosed between 2010 and 2012. The cases were classified based on estrogen receptor (ER), progesterone receptor (PR) and HER2 status as follows: ER and/or PR positive and HER2−; ER and/or PR and HER2 +; ER−, PR−, and HER2 +; and triple negative (ER−, PR−, and HER2−). We sought the association between the subtype and race, which is categorized as non-Hispanic (NH) white, NH black, NH Asian Pacific Islander (API) and Hispanic men. Results: We identified 1515 cases of male breast cancer diagnosed during the study period; 188 were excluded because of unknown race or subtype, and the remaining 1327 were included in our final cohort. 96.8% of cases were ER positive and less than 3.2% of cases were ER negative. 1145 patients (86.1%) were HR+/HER2-, 139 patients (10.0%) were HR+/HER2+, 12 patients (0.7%) were HR-,HER2+, and 31 patients (2.3%) were triple negative (Table 1).Tumor subtype did not vary by race/ethnicity (p = 0.08). Conclusions: Our results indicate that unlike female breast cancer that male breast cancer subtype does not vary by race/ethnicity. Further research is warranted to determine how these findings may impact the treatment and prognosis of male breast cancer. [Table: see text]
Breast cancer method of detection, stage at diagnosis, and delay in treatment in La Libertad province, Peru.
Authors: Romanoff Anya , Cedano Guadiamos Manuel , Hayes Constant Tara , Burga Vega Ana Maria , Zunt Joseph , Johnson Kay
Published: February 2017

15

Background: The majority of breast cancer deaths occur in low- and middle-income countries, as a result of late stage disease presentation and inadequate access to diagnosis and treatment. Delay from development of symptomatology to initiation of treatment is associated with more advanced breast cancer, and delays greater than three months have been associated with reduced survival. We investigated method of detection, disease stage, and time to diagnosis and treatment in breast cancer patients in Peru. Methods: This investigation was conducted at the Instituto Regional de Enfermedades Neoplasicas del Norte, in Trujillo, Peru. All women with a pathologic or clinical diagnosis of breast cancer who visited a breast surgeon from February-May 2015 were eligible to participate. Trained personnel conducted individual patient interviews in Spanish, utilizing a validated breast cancer delays questionnaire. Results: Of the 159 women who qualified for inclusion, 113 (71%) agreed to participate in the study. Mean age was 54 years (range 30-85). Patients lived an average of 3 hours from the oncology institute (range 0-36). Most households earned less than minimum wage, and most (66%) were covered by Seguro Integral de Salud, the government-funded medical insurance for citizens with limited financial resources. One hundred and five (93%) participants reported initially detecting their breast cancer as a result of symptoms. One cancer (1%) was detected during screening clinical breast examination, and 7 (6%) by screening mammography. Ninety-three patients had available stage at time of diagnosis, with the following distribution: stage 0- 2%, stage 1-3%, stage 2-44%, stage 3-48%, and stage 4-3%. Based on patient report, mean patient delay (symptom development to first medical visit at any facility) was 211 days. Mean provider delay (first medical visit until treatment initiation) was 241 days. Mean total delay (symptom development to treatment initiation) was 407 days. Conclusions: Almost all study participants initially detected their breast cancer as a result of symptoms. More than half presented with stage 3 or 4 disease. Average delay from symptom onset to start of treatment was greater than one year.
Frequency and predictors of insufficient chemotherapy use among stage I-III breast cancer patients by molecular subtype.
Authors: Zhang Lu , Ferguson Tekeda Freeman , Wu Xiao-cheng , Hsieh Mei-Chin , Fontham Elizabeth , Loch Michelle Marie , Yu Qingzhao , Chen Vivien
Published: February 2017

154

Background: Identification of distinct molecular subtypes has expanded the treatment options for breast cancer, however, chemotherapy remains the common and effective treatment for each subtype. The objective is to compare the frequency and predictors of insufficient chemotherapy use among two subtypes of stage I-III breast cancer patients: luminal A and triple negative breast cancer (TNBC). Methods: We analyzed data from a CDC funded project - Enhancing Cancer Registry Data for Comparative Effectiveness Research (CER) collected by Louisiana Tumor Registry. Women aged < = 70 years, diagnosed in 2011 with stage I-III luminal A or TNBC breast cancer, tumor size > 1cm, were included (N = 1,189). Insufficient chemotherapy (i.e. no chemotherapy use, nonstandard regimen use, and low relative dose intensity (RDI < 85%)) was evaluated respectively. Potential predictors included age, race, insurance, marital status, census tract-poverty, AJCC stage, grade, tumor size, lymph node status, and Charlson comorbidity. Stepwise model selection with p-value for entry at 0.2 and for stay at 0.25 was used to select the most relevant predictors. Results: The frequencies of no chemotherapy use were significantly different (p < .0001) between luminal A (42%, N = 913) and TNBC patients (9%, N = 241). Older age, white race, no insurance, lower stage or grade, and without lymph node involvement were related with no chemotherapy for luminal A patients; older age, not married, and high poverty for TNBC. There were 36% of luminal A and 40% of TNBC patients receiving nonstandard regimen (p = 0.27). Predictors of nonstandard regimen use were increased age, insurance, stage, and grade for luminal A and high poverty level and stage for TNBC. Reduced RDI occurred in 9% luminal A and 10% TNBC patients (p = 0.61). Small cases precluded the prediction model for low RDI. Conclusions: Luminal A patients are less likely to receive chemotherapy than TNBC patients. Low social economic status factors are associated with no chemotherapy use and nonstandard regimens use, especially for TNBC patients.
Tumor infiltrating lymphocytes (TILs) and the expression of programmed death ligand 1 (PD-L1) as predictors for the response rate of preoperative systemic therapy (PST) and prognosis in triple-negative breast cancer (TNBC).
Authors: Tomioka Nobumoto , Azuma Manabu , Hagio Kanako , Ikarashi Mayuko , Satoh Masako , Yamamoto Mitsugu , Watanabe Ken-ichi , Yamashiro Katsushige , Takahashi Masato
Published: February 2017

157

Background: The status of tumor infiltrating lymphocytes (TILs) is known to be prognostic for triple negative breast cancer (TNBC) due to its correlation with chemosensitivity. Moreover, to regulate the pathway of immune-checkpoint molecules is also expected to improve the prognosis of TNBC. The relevancy of these two factors could be attractive concerning on the immune interaction which might play an important role in the prognosis of TNBC. Methods: Patients with TNBC are 277 among 2371 who were underwent surgery between January 2002 and December 2011. Out of 90 patients received preoperative systemic therapy (PST), 32 patients’ specimens of core needle biopsy were available for review for TILs. The TILs was scored as “% stromal” by pathologist who feels comfortable with through the scan for single whole section according to the recommendations by an International TILs Working Group 2014. The expression of programmed death ligand 1 (PD-L1) was assessed by immunohistochemistry, which was defined 3 stages as negative or positive (weak or strong) by the pathologist in our facility. The statistical analysis for variance was done by Mann-Whitney U-test or Kruskal-Wallis test, and for survival by Kaplan Meier method was evaluated by Logrank test. Results: TILs’ score was defined as follows (%; numbers of patients): (5; 2), (10; 8), (20; 9), (30; 7), (40; 1), (50; 1), (60; 1), (70; 2), (80; 0), (90; 1). Statistical validations for variance of TILs’ score were significant on the regression rate of tumor size: (T-pT)/T; < 2/3 v.s. 2/3 < (p= 0.0097), and pathological therapeutic grade: 1 vs 2 or 3 (p= 0.0285). When we set the threshold at 30% of TILs’ score, DFS with TILs’ score < 30% was worse significantly (p= 0.0383) but not on OS (p= 0.0772). Unfavorable group on DFS (TILs’ score < 30%) was divided again into two groups by the status of PD-L1 significantly (negative or weak v.s. strong; p= 0.0319). Conclusions: The status of TILs and PD-L1 could elucidate the candidate for the therapeutic approaches to immune-checkpoint molecules, which could make improvement of the prognosis of TNBC.
Survival outcomes in Egyptian patients with triple-negative breast cancer: Single institute experience.
Authors: Jomaa Mona Kamal , Nagy Ahmed Aly
Published: February 2017

158

Background: Triple-negative breast cancer (TNBC) is a unique subtype and consider as an aggressive disease without established targeted treatment options. This study conducted to determine the incidence, characteristics, and survival outcomes of TNBC patients in an Egyptian cancer institute. Methods: Medical records of 520 patients treated between 2010-2011 in Clinical Oncology Department-Ain Shams University-Egypt were analyzed. Cox proportional hazards models were used to evaluate the association between TNBC and DFS and OS after adjusting for other covariates. Results: Among the 520 patients, 139 were TNBC .The median age was 50 years (SD±11.767, Range 20-80 ) versus 52 years (SD±12.134, Range 20-80), median tumor diameter was 5 cm (SD± 1.408, Range 1-7) versus was 5 cm (SD± 1.401, Range 1-7) , and median number of positive axillary LN was 3 (SD± 4.779, Range 0-37) versus 3 (SD± 4.832, Range 0-25) in non TNBC and TNBC respectively . Median disease-free survival was 24 months (SD± 14.128, Range 1-69 ) versus 15 months (SD± 8.811, Range 1-43 ) and median overall survival was 41 months (SD± 16.249, Range 3-60) versus 31 months (SD± 12.184, Range 7-60 ) in non TNBC and TNBC respectively. About 85.6 % of the TNBC tumors were IDC, 4.4 % were ILC and 5% were mixed. About 1.4 % of the TNBC tumors were grade I, 70.5 % were grade II and 28.1% were grade III. Median disease-free survival was 24 months (95%CI 21.679- 26.321) versus 15 months (95%CI 12.587-17.413) (p< 0.001) and median overall survival was 44 months (95%CI 41.396-46.604) versus 31 months (95%CI 29.460-32.540) (p< 0.001) in non TNBC and TNBC respectively. In TNBC cohort , DFS was 12 months (95%CI 11.464-12.536) in patients with grade III tumors versus 25 months (95%CI 22.359-27.641 )in patients with other grades (p< 0.001), this was also reflected in OS as 29 months (95%CI 25.129-32.871 ) versus 44 months (95%CI 41.238-46.762 ) (p< 0.001). Conclusions: Multivariate analyses supported a conclusion that TNBC subtype was an independent adverse prognostic factor for survival along with other known risk factors such as tumor grade.
Gene signature model for breast cancer risk prediction for women with sclerosing adenosis.
Authors: Radisky Derek C , Degnim Amy C. , Nassar Aziza , Stallings-Mann Melody , Anderson S. Keith , Oberg Ann L. , Winham Stacey J , Vierkant Robert A. , Frank Ryan D. , Wang Chen , Frost Marlene H. , Visscher Daniel W.
Published: February 2017

18

Background: Benign breast disease (BBD) is diagnosed in 1-2 million women/year in the US, and while these patients are known to be at substantially increased risk for subsequent development of breast cancer, existing models for risk assessment perform poorly at the individual level. Here, we describe a DNA-microarray-based transcriptional model for breast cancer risk prediction for patients with sclerosing adenosis (SA), a lesion found in ¼ of all BBD patients that is characterized by epithelial proliferation, disordered acinar architecture, and stromal fibrosis. Methods: A training set was developed from 86 patients diagnosed with sclerosing adenosis (SA), of which 27 subsequently developed cancer within 10 years (cases) and 59 remained cancer-free at 10 years (controls). A diagonal linear discriminate analysis (DLDA)-prediction model for prediction of cancer within 10 years (SA TTC10) was generated from transcriptional profiles of formalin fixed, paraffin-embedded (FFPE) biopsy-derived RNA. This model was tested on a separate validation case-control set composed of 65 SA patients. Results: The SA TTC10 gene signature model, composed of 35 gene features, achieved a clear and significant separation between case and control with receiver operating characteristic area under the curve of 0.913 in the training set and 0.836 in the validation set. Conclusions: Our results provide the first demonstration that benign breast tissue contains transcriptional alterations that indicate risk of breast cancer development, and that essential precursor biomarkers of malignancy are present many years prior to cancer development. Furthermore, the SA TTC10 gene signature model, which can be assessed on FFPE biopsies, constitutes a novel prognostic biomarker for patients with SA.
Modulation of breast cancer development in MMTV-PyVT mice by adiponectin: A perspective on tumor microenvironment.
Authors: Wang Yu
Published: February 2017

34

Background: The survival and growth of epithelial carcinoma cells are critically dependent on the interactions with the neighboring stromal cells. Adiponectin, a molecule exclusively produced by adipose tissue, possesses potent anti-inflammatory and anti-tumorigenic activities. Its expression and production are inversely associated with breast cancer risks in pre- and post-menopausal women. Reduced or completely loss of adiponectin expression enhances the development of mammary tumors in MMTV-PyVT mice. Despite these evidences, the mechanisms underlying the anti-breast cancer activity of adiponectin remain poorly understood. Methods: Adiponectin-deficient MMTV-PyVT mice that show distinct basal epithelial-like features of mammary tumors are used for analyzing the stromal vascular fractions (SVF) of the adipose tissues in tumor microenvironment. Results: Flow cytometric analyses demonstrate that adiponectin deficiency significantly alters the composition of cells in SVF isolated from the mammary adipose tissues. Adiponectin-deficient SVF contribute to the metaplastic features of the basal epithelial-like breast cancers. Co-implantation of SVF derived from adiponectin-deficient mice accelerates mammary tumor development and metastasis in NOD/SCID mice engrafted with MDA-MB-231 human breast cancer cells. Fluorescence Activated Cell Sorting isolates a population of CD44+CD25-CD100+ cells that are enriched in both thymus and SVF of mice lacking the expression of adiponectin. Upregulated CD100 expression interrupts early T-cell development and maturation. In mammary tissues, CD44+CD25-CD100+ cells facilitate the development of metaplastic basal epithelial-like breast cancers. Adiponectin treatment down-regulates CD100 expression, in turn enhancing Notch signaling and T-cell maturation in the thymus, and reduces the accumulation of CD44+CD25-CD100+ cells in the tumor microenvironment. Conclusions: These results support a pivotal role of adiponectin in mediating the epithelial-stroma crosstalk to prevent mammary carcinogenesis and shed new lights on the development of immuno-therapeutics for breast cancer diseases.
Does “two is better than one” apply to surgeons? Comparing single-surgeon and cosurgeon bilateral mastectomy outcomes.
Authors: Nimbkar Suniti , Mallory Melissa Anne , Losk Katya , Camuso Kristen , Golshan Mehra
Published: February 2017

35

Background: Bilateral mastectomies (BM) are generally performed by a single surgeon (SS). A two-attending ‘co-surgeon’ (CS) technique, in which each surgeon concurrently performs a unilateral mastectomy, offers an alternative operative approach. We sought to examine differences in general surgery time (GST), overall surgery time (OST), and patient outcomes for BM performed by CS and SS at our institution. Methods: Patients undergoing BM with tissue expander reconstruction (BMTR) between January 2010 and May 2014 at our institution were identified and divided into SS and CS cases. Operative records were used to calculate GST (incision to end of BM procedure), reconstruction time (plastic surgery start time to end of reconstruction) and OST (OST = GST + reconstructive time). Patient age, presence and stage of cancer, breast weight, axillary procedure [sentinel node biopsy (SNB) or axillary dissection (ALND)], and 30-day postoperative complications were extracted from medical charts. Differences in GST and OST between CS and SS performed cases were assessed using a t-test. A linear regression was performed to identify factors contributing to GST. Results: We identified 116 BMTR cases performed by 8 breast surgeons, [CS, n = 67 (57.8%); SS, n = 49 (42.2%)]. Demographic characteristics did not significantly differ between groups. In the bivariate analyses, GST and OST for CS cases were significantly shorter than for SS, 75.8 vs 116.8 minutes, p < 0.0001, and 255.2 vs 278.3 minutes, p = 0.005, respectively. The linear regression demonstrated a significant decrease in GST when BMTR was performed by CS (β = -38.82, p < 0.0001); total breast weight (β = 0.0093, p = 0.03) and axillary dissection (β = 28.69, p = 0.0003) were found to significantly impact GST. Conclusions: The GST of BMTR is significantly decreased using a CS-approach without impacting complication rates. However, the degree of GST and OST-reduction suggests the addition of a CS does not proportionally impact surgical time as would be expected. A CS-approach may be more beneficial for patients with large total breast weight or those requiring ALND. A larger study is warranted to better characterize time, cost, and outcomes of the CS-approach for BM.
Disease progression of metastatic breast cancer by first relapse site after definitive radiotherapy.
Authors: Shiraishi Kenshiro , Tada Keiichiro , Kawamori Jiro , Fukuuchi Atsushi , Nishi Tsunehiro
Published: February 2017

36

Background: Bone metastasis as initial distant relapse is commonly considered to have better prognosis than other sites in metastatic breast cancer. To elucidate true clinical course of metastatic disease, it is essential that we prospectively manage patients since primary setting. Methods: Overall, 3,417 patients with breast cancer treated with mastectomy (n = 379, 11.1%) or breast-conserving surgery (n = 3,029, 88.6%) followed by definitive radiotherapy at two institutions in Center of Tokyo between 1980 and 2014 were included in the study. Information on all patients was prospectively collected and rigorously-controlled. Initial metastatic relapse sites included bone, brain, and other (mainly visceral). Intrinsic subtypes of tumor were classified as luminal A, luminal-human epidermal growth factor receptor 2 (HER2), luminal B, triple negative, and HER2 identified by routine immunohistochemistry and histological grade. Cumulative incidence rates of overall survival (OS) for each affected site after metastatic relapse were estimated according to Kaplan-Meier method. Results: Median follow-up time for living patients was 113 months. A total of 370 patients experienced metastatic progression as first relapse event. Median duration of OS after initial metastatic relapse was 69 month in all subtypes. No difference was seen in OS among five subtypes after initial bone or brain relapse. Meanwhile, OS of luminal subtypes after initial other-site relapse was better than that of triple negative and HER2 subtypes (P = .003). Notably, OS rates of bone and non-bone/brain metastasis groups as initial relapse site were almost identical (P= .626). Conclusions: We find no difference in mortality after metastatic relapse between bone and other site except for brain metastasis as initial relapse in breast cancer patients following definitive radiotherapy in our cohort without primary metastatic setting. Careful consideration is needed for initial distant relapse regardless of which site is involved. However, prognosis of metastatic breast cancer after definitive radiotherapy is favorable based on real world data, attributable mainly to improved systemic therapy and modern multidisciplinary approach.
Tubular carcinoma of the breast: A single institution's experience of prognosis.
Authors: Boyan William P , Farr Michael , Shea Brian , Kohli Manpreet , Ginalis Ernest
Published: February 2017

37

Background: Tubular carcinoma is a less aggressive form of breast cancer which emcompasses 1-4% of invasive breast cancer. Prior studies have shown a nearly 100% 15 year survival rate for tubular carcinoma compared to the 89.2% five year survival of all breast cancers. The question asked is if these two cancers should be treated the same. The goal of oncologic treatment is to maximize survival while limiting side effects. At the very least, care givers should be able to give prognostic encouragement to patients based on this less aggressive histological subtype. Methods: A retrospective study of charts for tubular carcinoma of the breast from 2000 to 2015 were analyzed. A total of 57 patients were captured. All relevant aspects of the patients history, as well as therapies rendered and outcomes were documented. The aim of our study was compare treatment outcomes in our group of tubular carcinomas to that of breast cancer as a whole. Results: A total of 57 patients were diagnosed and treated for tubular carcinoma of the breast between 2000 and 2015 from a single institution. Of the 57 patients, local recurrence was seen in two patients. The first patient underwent lumpectomy, endocrine and radiation therapy then recurred as an invasive ductal carcinoma 12 years later. A second patient underwent lumpectomy with endocrine treatment but refused radiation, recurring as a tubular carcinoma 10 months later. In our 16 year sample the recurrence rate was 3.5% or 1.75% recurring as tubular. This is lower than the rates of recurrence of all breast cancer. To this date there were no cancer related mortalities in our group. Conclusions: A look into our institution’s data supported the notion that tubular carcinoma of the breast is a less aggressive histological type. Of our 57 cases and mean follow up time of six years ranging from one year to fifteen, only two recurrences (3.5%) were noted and there was no cancer related mortalities. Interestingly only one (1.75%) recurred as tubular carcinoma. Without controlling for adjuvant therapy, recommendations cannot be made for a less aggressive treatment plan at this point. Based on this study and others like it physicians can give evidenced based favorable prognosis when the diagnosis of tubular carcinoma is made.
A comparison of clinicopathological characteristics and survival outcomes between symptomatic and screen detected breast cancer in Japanese women.
Authors: Inari Hitoshi , Shimizu Satoru , Yoshida Tatsuya , Suganuma Nobuyasu , Yamanaka Takashi , Nakayama Hirotaka , Yamanaka Ayumi , Rino Yasushi , Masuda Munetaka
Published: February 2017

4

Background: In Japan from 2000, mammography screening has been introduced into the breast cancer screening for women aged 50 or above, however in the early 2000s, breast cancer screening involved palpation only and mammography combined. Only a few studies have been reported clinicopathological characteristics and survival outcomes of this screening detected breast cancer in Japan. This study evaluated effectiveness of this screening by comparing symptomatic and screen detected breast cancer Methods: From January 2000 to December 2004, 1159 patients were underwent surgery for treatment of breast cancer at single hospital in Japan. Among them, 977 patients were symptomatic and 182 patients were this screen detected, and follow-up was performed from the date of the diagnosis until the date of death or the end of follow-up, March 2015. We retrospectively reviewed the clinical and pathologic data. Results: Screen detected breast cancer was associated with more breast conservation surgery, smaller tumor size, less lymph node involvement, more hormone receptor positive, more non-invasive carcinoma and less adjuvant chemotherapy compared with symptomatic breast cancer (P < 0.05). In univariate analyses, women with screen-detected tumors had improved overall survival compared to women with tumors that were detected symptomatically (10-year OS: 90.6% vs.80.4%, P = 0.01). According to ages, in women older than 50 years women with screen-detected tumors had improved overall survival compared to women with tumors that were detected symptomatically (10-year OS:87.7%vs.76.7%, P = 0.006). Screen detection of all patients was independently associated with improved overall survival outcomes (HR 0.47, P = 0.002, respectively), screen detection in women older than 50 years was also similar (HR 0.494, P = 0.007, respectively). Conclusions: This study showed that early detection in breast cancer screening had led to increase in breast conservation rate, avoidance of axillary lymph node dissection, more hormone receptor positive, avoidance of adjuvant chemotherapy, and improvement of survival rate.
Pathologic complete response after neoadjuvant paclitaxel and carboplatin chemotherapy for stage II-III breast cancer: A community cancer center experience.
Authors: Belur Anuradha , Arumugam Raajasekar Arun Kumar , Burdette-Radoux Susan
Published: February 2017

43

Background: To evaluate the efficacy and safety of neoadjuvant carboplatin and weekly paclitaxel in locally advanced breast cancer. Methods: In a retrospective study, 15 patients receiving neoadjuvant chemotherapy with carboplatin and paclitaxel from 2008 to 2013 were identified with breast cancer stages IIA to IIIB. Patients received carboplatin at 6 times the area under the curve (AUC 6) every 4 weeks and paclitaxel 80 mg/m2 weekly for 16 weeks. Weekly trastuzumab was added for human epidermal growth factor receptor 2 (HER2) positive status. The primary endpoint was pathologic complete response (pCR) rate, defined as the absence of invasive cancer in breast and axillary lymph nodes. Partial response was defined as downstaging from clinical to pathologic stage. Results: 15 patients were identified. Median age was 57 years (range, 33 to 80 years). 6 women were African American, 3 Hispanic, 2 Asian and 3 Caucasian. 4 patients had stage IIIB disease, 5 had stage IIIA, 5 had Stage IIB and one had stage IIA. 2 patients had inflammatory cancer. 8 patients underwent modified radical mastectomy, 2 bilateral mastectomy and 4 lumpectomy. The tumor was estrogen receptor positive (ER+) in 8 patients, triple negative in 7 patients and HER2 positive in 2 patients. There were two episodes of febrile neutropenia and one death from sepsis. There was one episode of grade 4 thrombocytopenia requiring dose reduction of carboplatin to AUC 4. There were two instances of grade 3 peripheral neuropathy. One of these patients received a dose reduction of paclitaxel to 70 mg/m2. 10 patients received additional dose dense chemotherapy with doxorubicin and cyclophosphamide. Overall, the pCR rate was 0. Partial response was seen in 9 patients (60%). 14 patients received postoperative radiation; one patient declined radiation therapy. Conclusions: In cooperative group trials, neoadjuvant carboplatin and paclitaxel has been shown to achieve high pCR rates in patients with triple negative and HER2 positive breast cancer without exposure to an anthracycline. In our ethnically diverse patient population at a community cancer center, no pathologic complete responses were seen.
Accelerated partial-breast irradiation (APBI) versus whole-breast irradiation (WBI) in treatment of the biological subtypes of breast cancer: An analysis of comparative effectiveness.
Authors: Chen Peter Y. , Wallace Michelle , Ye Hong , Wobb Jessica , Jawad Maha Saada , Dekhne Nayana , Brabbins Donald S.
Published: February 2017

45

Background: To assess if partial vs whole breast irradiation (RT) in treatment of the various biological (bio-) subtypes of breast cancer would lead to differing clinical results, a match pair analysis of APBI vs WBI was undertaken. Methods: Between 3/1993 and 9/2013 all breast CA patients (pts) treated at one institute with either APBI or WBI were matched 1:1 by follow-up (FU) +/- 15 yrs, stage and bio-subtype. This yielded 772 pts of whom 640 were luminal A, 42 luminal B, 58 triple neg (TNBC), 6 HER2+, and 26 triple +. Outcomes were analyzed across the various bio-subtypes for all the pts (APBI + WBI), APBI alone and WBI alone. The endpoints assessed were local recurrence (LR), true recurrence/marginal miss (TR/MM), elsewhere failure (EF), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), and contralateral breast failure (CLBF). Results: Mean age was 66 (32-94) with a mean FU of 5.2 years (0.1-18.3). Regarding systemic therapy, 75% received endocrine Rx, while chemotherapy was documented in 21%. For all pts (APBI+WBI) there was no significant difference across the various bio-subtypes with respect to 5, 10 and 15 yr actuarial LR, TR/MM, EF, RR, DM, DFS and CLBF. Likewise, for the 386 APBI-alone treated pts, no significant difference was found between the various bio-subtypes for all the same endpoints reported. However, for the 386 WBI pts, a significant difference was seen in the 15-year actuarial LR between luminal A and TNBC (1.5% vs 7.4%, p = 0.007). Significance was also found in the 15-year actuarial DFS between luminal A/B and TNBC (98.0%, 95.2%; 86.0%, respectively, p = 0.009). Conclusions: In comparing partial to whole breast RT across the various biological subtypes of breast CA, APBI is at least as effective as WBI. However, the retrospective nature of this study along with the limited numbers of pts in the HER2+ and triple + subsets are weaknesses which are acknowledged to exist in this dataset. The addition of further pts in all the biological subtypes, particularly the HER2+ and triple + subsets, along with results from randomized trials incorporating biomarker data will be needed to substantiate these findings.
Intraoperative margin assessment with the MarginProbe at different mammographic breast densities.
Authors: Police Alice , Lin Erin , Lane Karen
Published: February 2017

47

Background: Mammographic breast density (BD) is known to affect breast imaging. MarginProbe is an RF Spectroscopy intraoperative margin assessment tool. We looked at the effect of mammographic breast density (BD) on the performance of the device. Mammographic density was assigned by Breast Imaging-Reporting and Data System (BI-RADS) classification prior to breast conserving surgery with the MarginProbe. Methods: For the current study we analyzed MarginProbe device arm data from the MarginProbe Pivotal Trial for which BD data was available. Clear margins of the main specimen, which is where the MarginProbe was applied, were defined as no tumor on ink. Clinical benefit was defined as clearing positive main specimen margins or cancer in the shaving. Analysis was performed based on logistic and linear regression, with univariate analysis. Results: The dataset for the analysis included 196 patients for which preoperative BD data was available. With higher BD, there was an increase in the rate of main lumpectomy specimen with positive margins (OR 1.65 per change in density category, p=0.025). The rate of shavings with clinical benefit showed an upward trend, with increasing BD. The number of shavings per patient increased with BD, however the overall volume of shavings did not increase. There was an increase in the per patient relative clinical benefit as BD increased (OR 1.6 per change in density category, p=0.024). Conclusions: With higher breast density patients and surgeons face an increase in risk for main specimen positive margins. With the increased BD and main specimen positivity more shavings were removed, but shavings volume did not increase as average shaving volume decreased with higher BD. Higher level of patient clinical benefit was observed with higher BD.
Assessing the value of hepatic arterial phase CT imaging in patients with breast cancer.
Authors: Motiuk David , Ng Danny
Published: February 2017

5

Background: Hypervascular liver metastases, classically seen in melanoma and other cancers, may be best seen on a hepatic arterial phase (HAP) CT and possibly missed on the standard portal venous phase (PVP). Breast cancer sometimes produces hypervascular liver metastases, but the incidence of this is not well established. Hence, some centers perform biphasic liver CT (HAP + PVP) as standard protocol in breast cancer patients, while others do not. Our center does not include HAP in this patient population; although, it is sometimes protocolled with HAP as per radiologist preference. We sought to determine if the detection for presence or absence of liver metastases is significantly affected by the addition of HAP in breast cancer. Methods: This retrospective study was conducted using a custom search on our Picture Archiving and Communication System for all female patients who received a biphasic liver CT (HAP + PVP) from Mar 2013 - Mar 2015. Inclusion criteria included known breast cancer, liver metastases described on CT report, and follow-up imaging to confirm the finding. A total of 25 CT studies met inclusion criteria. Results: 14/25 (56%) studies demonstrated typical non-hypervascular hepatic metastases. 11/25 (44%) demonstrated hypervascular hepatic lesions. Of these latter, 4/25 (16%) represented hypervascular metastases, while 7/25 (28%) pertained to indeterminate arterial-enhancing lesions called suspicious by the reporting radiologist. Further imaging including MRI, ultrasound, and follow-up CT were recommended in these indeterminate suspicious lesions, all of which confirmed benign entities. Of the 18 studies with true hepatic metastases, the presence of metastatic disease was detectable on the PVP in 18/18 (100%, P< .0001) regardless of the metastases’ hypervascular status. Conclusions: We found hypervascular metastases to be present in 22% (4/18; CI95 [3-41%]) of breast cancer patients with true liver metastases. However, the detection for the presence of hepatic metastases was not improved with the addition of HAP. The HAP instead led to detection of more indeterminate but ultimately benign entities of no clinical significance, thus resulting in unnecessary imaging and arguably greater patient anxiety.
Breast density and the risk for positive lumpectomy margins.
Authors: Schnabel Freya Ruth , Allweis Tanir
Published: February 2017

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Background: Current methods for intraoperative assessment of lumpectomy margins are limited, and a meaningful proportion of patients require re-excision to achieve acceptable margins. There is little available information regarding the relationship of mammographic breast density (BD) and positive margin rate. Methods: The MarginProbe device uses radiofrequency spectroscopy to evaluate the margins of lumpectomy specimens. The current study utilized data from the MarginProbe Pivotal Trial (Dune Medical Devices, Israel, NCT00749931). This randomized clinical trial compared adjunctive intraoperative use of the MarginProbe device with surgeons’ standard approach to lumpectomy surgery. For the current analysis, data was compiled from the period prior to patient randomization and device use. Variables of interest included BD, patient and tumor characteristics, and the margin status of the main lumpectomy specimen (prior to device use in the device arm). For the purpose of this analysis, a positive margin was considered tumor on ink. Statistical analysis was performed with univariate and multivariate analysis, and linear/logistic regression. Results: A total of 664 patients were enrolled in the trial. 450 patients had preoperative breast density information available, and formed the basis for this analysis. As expected, higher BD was associated with younger age, lower BMI and smaller breast and specimen volume. Increased BD was also associated with increased use of preoperative MRI imaging (odds ratio 2.2, p<0.0001). Higher BD was also associated with a significant increase in main lumpectomy specimen positive margin rate (Table). The odds ratio was 1.46 per change in density category (p=0.011). BD remained significantly associated with positive margins after controlling for age, BMI and breast volume. Conclusions: Higher BD is an independent risk factor for positive margins in main lumpectomy specimens, suggesting that adjunctive methods for intraoperative margin assessment may be particularly helpful in these patients. [Table: see text]
Avoiding skin creams right before radiation: Myth or sound advice?
Authors: Baumann Brian C. , Verginadis Ioannis I , Zeng Chuan , Vachani Carolyn , Solberg Timothy , Koumenis Costas , Metz James M.
Published: February 2017

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Background: Radiation dermatitis in breast cancer patients is common and often treated with topical creams. Patients are traditionally advised to avoid lotions for several hours before radiotherapy (RT) based on concern that creams might increase skin dose. With modern RT’s improved skin sparing, this recommendation may be irrelevant. We hypothesize that applying either metallic or non-metallic creams before treatment would have minimal effect on skin dose. Methods: We conducted an online, 24-question OncoLink survey of patients and providers to determine current skin cream practices. To evaluate the dosimetric effect of creams, we delivered 200 MU at 100 cm SSD and measured the dose at the surface and 2 cm depth in a tissue equivalent phantom, with or w/o 2 common skin creams, Aquaphor and silver sulfadiazine. We assessed the effect of various photon and electron energies, cream thicknesses and beam incidence on dose. The effect of creams on skin dose was also evaluated in C57BL/6 mice using γ-H2AX IHC staining. Results: 27 of 33 surveyed breast cancer patients (82%) and 43 of 45 providers (96%) either received or gave the advice to avoid applying creams prior to RT treatments. Measurements showed no difference in dose at the surface or 2 cm depth with or w/o a 1-2 mm application of either cream when using enface 6 or 15 MV photons. The same application of cream had no effect on surface dose as a function of beam incident angle from 15-60°, except for a 7% increase at 60° with the silver cream. Surface dose for 6 & 15 MV beams were significantly increased with a thicker (≥3 mm) layer of cream. For 6 MV, the surface dose was 105 cGy (Aquaphor), 102 cGy (silver cream) and 88 cGy (controls). For 15 MV, the doses were 70, 60 and 52 cGy. With 6 and 9 MeV electrons, there was only a 2-5% increase in surface dose with use of creams. There were no dose differences at 2 cm depth. Irradiated skin in mice showed no difference in γ-H2AX positive foci with or w/o creams. Conclusions: This is the first dosimetric assessment of the effect of skin creams for RT dermatitis. Our findings suggest that thin or moderately applied creams, even if applied just prior to RT, have minimal impact on skin dose, regardless of beam energy or beam incidence. Applying very thick amounts of cream just prior to RT increased surface dose and should be avoided.
Clinical use of a three-dimensional tissue marker to target postlumpectomy radiation.
Authors: Kaufman Cary Steven , Hall William H. , Wolgamot Greg M , Hill Laurie , Caro Rebecca , Nix Sid , Evans Erik , Zacharias Karen , Mahon Carol , Ness Karen , Schnell Nancy , Schnell Nancy
Published: February 2017

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Background: A three dimensional bioabsorbable coiled tissue marker has been developed to facilitate targeting for radiation therapy post lumpectomy. Proposed advantages are a) clarified targeting of closest margins to the excised tumor, b) providing a three dimensional structure that allows fibrosis to add volume to contribute to cosmesis, c) aiding in re-excision localization. Our experience has demonstrated the array of clinical findings after placement, the imaging findings over time, and pathologic findings for early and late removal. Methods: Consecutive lumpectomy patients who were candidates for targeted radiation therapy were implanted with the 3-D bioabsorbable marker from May 2014 to June 2015. After informed consent, each of 36 patients were followed to gather clinical, imaging and pathologic findings. Standard breast cancer management decisions were made (NCCN). Patients requiring re-excision were examined for pathologic findings related to the device. Routine imaging with mammography and ultrasound were obtained at 6 and 12 months post lumpectomy. Results: The use of the spiral tissue marker with the fixed array of six titanium clips provided a predictable target for radiation treatments. As the tissue marker was sewn to the closest tumor bed, inadvertent dissection planes caused by oncoplastic techniques could be avoided. Clinically the lumpectomy site was firm/dense in 94% of patients at 3 months (n = 36), but in only 60% at one year (n = 21). Two patients who underwent re-excision for positive margins were guided by the 3-dimensional device. Two patients had removal at one month and at 12 months for reasons unrelated to the tissue marker. Histologic examination demonstrated typical foreign body reaction and organization (fig 1b). Mammography at one year demonstrated marker clips coalescing as the bioabsorbable device dissolves with maintenance of the volume of the cavity in 50% of patients(fig 1c). Cosmetic outcome has been good to excellent measured at 6 and 12 months. Conclusions: Clinical, radiologic and pathologic findings during use of a novel bioabsorbable 3-dimensional tissue marker were presented. A national registry to further define these attributes will soon be started.
The association of clinical-pathologic factors and Oncotype Dx recurrence score (RS) in the outcome of early stage breast cancer.
Authors: Chadha Manjeet , Stewart Robert , Wallach Jonathan
Published: February 2017

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Background: Oncotype Dx recurrence score (RS) is routinely used to guide systemic therapy based on the estimated risk for distant relapse. Patients with early stage disease are also at risk for locoregional recurrence, and in some instances local relapse is the only site of failure. The objective of this study is to evaluate patient outcomes in association with known clinical-pathologic risk factors and RS. Observations in context of known clinical-pathologic features and RS may have important clinical implications relative to adjuvant locoregional therapy. Methods: This is an IRB approved retrospective study that includes patients with unilateral breast cancer and in whom the RS was reported. A total of 716 patients met this defined criteria. Seventy two percent underwent breast conserving therapy (BCS) and 28% underwent mastectomy; 68% had stage I and the remaining had > Stage II disease.The clinical-pathologic variables including age, stage, BRCA mutation, extent of surgery, and RS were studied in evaluating patient outcomes. Results: The median age was 56 years (27 to 84 years). The overall distribution of RS reported as low (18), intermediate (19-30), and high ( > 31) was 59%, 31%, and 10%, respectively. This distribution ratio was no different among patients treated with BCS and mastectomy. However, among BRCA mutation carriers there was a higher incidence of the high RS.Overall, the median follow up was over 3 years, and 25% of the patients have been followed over 5 years. The 3-year and 5-year any relapse-free survival was 93% and 89%, respectively. Age was significantly associated with observed inferior any relapse-free survival; 85% and 91% in women < 40 years vs > 40 years, respectively (p = 0.018). On univariate analysis, RS had no significant association with local regional relapse free survival. Further, associations between the clinical-pathologic features and RS using multivariate analysis will be presented. Conclusions: Observations with early follow up do not suggest a select role of RS in guiding risk tailored local regional therapy. Longer follow will further our understanding of patients at risk for local regional relapse.