bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.