bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathologic characteristics of breast cancer with special emphasis on prevalence of triple-negative breast cancer from Kenya: A 4-year experience.
Authors: Sayed S. , Moloo Z. , Mukono S. , Wasike R. , Chauhan R. R. , Ndonga A. , Trinkaus M. E. , Rahim Y. , Wedad H. , Saleh M. N. 
Published: February 2017

35 Background: Previous sub classification of breast cancer in Kenya has been fraught by small sample size, non uniform staining methodology and lack of independent review. Triple Negative Breast Cancer (TNBC) is a “special interest” cancer since it represents a significant proportion of breast cancer patients and is associated with a poorer prognosis. We aimed to determine the estrogen receptor (ER), progesterone receptor (PR) and Her2/neu receptor characteristics of breast cancers and the prevalence of TNBC diagnosed at Aga Khan University Hospital, Nairobi (AKUHN) between 2007 to date. Methods: Slides and blocks of archived invasive breast cancers diagnosed at AKUHN were identified, retrieved and reviewed by two independent pathologists. Histological type, grade and pathological stage were documented. Representative sections from available blocks were stained for ER, PR, Her2 with appropriate internal controls. Scores for ER/PR were interpreted based on the ALLRED system, Her2 /neu scoring followed CAP guidelines. The initial 111 cases were validated and confirmed at Sunnybrook Health Sciences Centre, Toronto. Results: 456 cases of invasive breast cancers were diagnosed at AKUHN during the study period. 91% of cases were invasive ductal carcinomas (NOS).The rest were special types. 37% of the tumors were grade 3 and 63% were grade 2. Blocks for 318 of 456 cases were available for receptor analysis. 54% were ER and/or PR positive, with 52% of these in women < 50 yrs. 86% of the ER and/or PR positive tumors were grade 2. Only 12% were Her2/neu positive. Of the 318 cases studied, 111 (32%) were identified as TNBC. Median age was 53 yrs. 88% were grade 3. Conclusions: Invasive ductal carcinoma (NOS) was the most common breast cancer in our study. Nearly half of our cases were ER and/or PR positive and a third were TNBC. Both occurred predominantly in women less than 50 yrs. This represents the largest validated pathologic sub classification of breast cancer from a tertiary academic hospital in Kenya. Expansion of this study to encompass all breast cancers diagnosed in Kenya is underway.
Prognostic role of triple-negative subtype in breast cancer patients with brain metastases.
Authors: Mathew A. , Rosenzweig M. Q. , Brufsky A. 
Published: February 2017

36 Background: Metastatic breast cancer (MBC) patients with brain metastases (BM) have a poorer prognosis compared to patients with metastases to sites such as bone or other visceral organs. The role of breast cancer subtypes such as triple negative (TN) status and its relationship with other known prognostic factors have not been well delineated in the context of metastatic disease to the brain. We conducted a retrospective single institution cohort study of MBC patients with BM to evaluate the association between TN subtype and overall survival from the diagnosis of BM. Methods: Baseline demographic and tumor specific data including ER, PR and HER2 status were collected on newly diagnosed MBC patients between January 1998 and December 2009. Overall survival was determined from the date of diagnosis of BM. Survival analyses were performed using the Kaplan-Meier method and Cox proportional-hazards model. Results: Data were available on 186 MBC patients with BM, of whom 156 died during a median follow-up of 10.2 months from the diagnosis of BM; median age was 47.9 years. 91% of patients were Caucasian; 25.3% had triple negative disease. Median survival from the period of diagnosis of BM in patients with triple negative disease was 7 months (Interquartile range, IQR: 3–13) as compared to 11 months (IQR: 5–22) in patients who were HER2-positive or ER/PR-positive. Multivariate analysis found a higher risk of death after BM for TN disease subtype, with a hazard ratio for death of 2.89 (95% confidence interval: 1.89–4.44; p<0.001), when adjusted for variables such as age and stage at initial diagnosis of breast cancer, race, the number of metastatic sites, and the use of metastatic chemotherapy. The administration of metastatic chemotherapy had a significant survival benefit in the analyses, with a hazard ratio for death of 0.52 (95% CI: 0.27–0.99; p=0.048). Conclusions: This retrospective cohort study in MBC patients with BM provides evidence for a greater risk of death in those with TN disease as compared to HER2-positive or ER/PR-positive subtypes even after adjusting for other prognostic factors.
Long-term outcome of DCIS patients: p53 as a biomarker of ipsilateral recurrence.
Authors: Hieken T. J. , Krishnamurthy V. , Farolan M. , Velasco J. M. 
Published: February 2017

39 Background: Ductal carcinoma in situ (DCIS) is a heterogeneous and potentially curable disease with a long natural history. DCIS represents 21% of breast cancers diagnosed in 2010. The risk of dying after a diagnosis of DCIS is low, emphasizing the importance of treatment-related morbidity, yet the risk of recurrence remains substantial. Optimum individualized therapy remains elusive. We previously identified p53 overexpression as a biomarker for ipsilateral tumor recurrence (IBTR). The purpose of the current study was to investigate its prognostic validity in an expanded patient cohort with long-term follow-up. Methods: We studied 186 consecutive pure DCIS patients from our Breast Cancer Registry and identified 142 cases with sufficient histopathologic material to perform evaluable immunostaining for p53. Median follow-up was 11 years. Statistical analysis was performed with SAS software. Results: Median patient age was 66 (range 35-91) years and 47/153 (31%) presented with palpable disease. Median tumor size was 10 (range 2-165) mm. Predominant histologic subtype included 34 (24%) comedo, 43 (30%) solid, 50 (35%) cribiform and 15 (11%) micropapillary/papillary cases. Necrosis was present in 74/142 (52%) of tumors. Overexpression of p53 was identified in 33/142 (23%) and was associated with necrosis, but not with any other patient, tumor or treatment variables. Fifteen patients (11%) were diagnosed with an IBTR at a median of 56 (range 11-154) months after their initial diagnosis; 3 recurrences were DCIS, while 12 were invasive cancer. p53 overexpression, present in 10/15 (68%) of cases with recurrence versus 23/127 (18%) of non-recurrent tumors, p < 0.001, and no adjuvant tamoxifen, p = 0.003, were associated with IBTR. No other patient, tumor or treatment factors studied were predictive of IBTR. The type of IBTR did not correlate with the p53 status of the index tumor. Conclusions: These data suggest that p53 may be a biomarker for elevated risk of IBTR after a diagnosis of DCIS and support the value of adjuvant tamoxifen for DCIS patients. Further investigation to validate these findings and to identify clinically useful individualized risk stratification for DCIS patients is warranted.
The novel cytotoxicity of neutrophils in the peripheral blood of breast cancer patients versus women without breast cancer.
Authors: Granot Z. , Comen E. A. , Norton L. , Benezra R. 
Published: February 2017

44 Background: Using murine mammary tumor models, recent research conducted by our laboratory at the Sloan-Kettering Institute indicates that select neutrophils are mobilized and entrained by a primary breast tumor and uniquely have the capacity to inhibit metastatic seeding in the lung (Granot Z et al. unpublished). We sought to determine whether entrainment of cytotoxic neutrophils also occurs in blood samples from women with newly diagnosed breast cancer as contrasted to those garnered from healthy women. Methods: Subjects were 21 newly diagnosed pre-operative breast cancer patients without evidence of metastatic disease, 9 healthy female volunteers with no history of any cancer, and 3 patients with newly diagnosed DCIS. Neutrophils were purified from the blood samples. Cytotoxicity was evaluated by incubating isolated neutrophils with luciferase labeled MDA-MB-231 cells. Luciferase activity, as a reflection of % cell kill, was measured using a Bio-Tek microplate luminescence reader. Results: Significant cytotoxicity was notably observed when MDA-MB-231 cells were co-cultured with neutrophils purified from patients with invasive tumors. Pre-operative breast cancer patients (n=21) had a cell kill range of 0-30% (mean = 12.1%), whereas healthy subjects (n=9) had a cell kill range of 0.2-8% (mean = 2.6%), p<0.004. DCIS patients (N=3) had a cell kill range of 3-4% (mean = 2.7). Conclusions: To date, this preliminary work is the first to demonstrate the cytotoxic role of select neutrophils in the peripheral blood of breast cancer patients as contrasted with those from women without breast cancer. Further studies are needed to evaluate the prognostic and therapeutic role of cytotoxic neutrophils.
Effect of cyclooxygenase inhibition on CXCR3 ligand secretion in breast cancer.
Authors: Bronger H. , Kraeft S. , Stöckel A. , Welk A. , Kiechle M. , Schmitt M. , Schwarz-Boeger U. R. M. 
Published: February 2017

45 Background: In murine cancer models, the two IFN-γ inducible chemokines CXCL9 and CXCL10, those bind to the common receptor CXCR3, recruit NK cells and tumor-suppressive lymphocytes into the tumor site and impair tumor growth and metastatic spread. In human breast cancer (BC), we and others have shown that high levels of CXCL9 mRNA correlate with favorable prognosis and the number of infiltrating lymphocytes. Raising the intratumoral level of CXCR3 ligands might therefore be a feasible way to enhance the infiltration by tumor-suppressive immune cells and to improve immune intervention in breast cancer. Inhibition of cyclooxygenases (COX) has been shown to inhibit tumor growth and metastases formation in a lymphocytic and IFN-γ dependent manner. We therefore tested whether COX inhibition induces CXCR3 ligand secretion from breast cancer cells. Methods: Human MCF-7 and MDA-MB 231 BC cells were stimulated with IFN-γ with or without prostaglandin E2 (PGE2) or COX inhibitors (indomethacin, aspirin, celecoxib). CXCL9 and CXCL10 release was measured by ELISA. COX-1 and COX-2 expression was measured in 45 BC samples and correlated with intratumoral CXCR3 ligand concentration. Results: Prostaglandin E2 inhibits CXCL10 and CXCL9 release from breast cancer cells. Aspirin and indomethacin enhance the INF-γ mediated secretion of these CXCR3 ligands by inhibition of endogenous cyclooxygenases. Celecoxib has this effect only at low concentrations, at higher concentrations is shows PGE2 agonistic effects. In human breast cancer samples, COX-2 overexpression inversely correlates with CXCR3 ligand concentration, which shows that the mechanism of PGE2 induced CXCL9/CXCL10 suppression might also be relevant in vivo. Conclusions: Suppressing endogenous PGE2 by cyclooxygenase inhibition increases CXCL9 and CXCL10 release from breast cancer cells and is therefore a feasible way to enhance the infiltration of breast tumors by tumor-suppressive lymphocytes. However, our results show that unselective COX inhibitors might be more suitable than the COX-2 specific celecoxib. Clinical trials are now warranted to clarify the mechanisms and therapeutic efficacy of COX inhibition in breast cancer.
Lobular neoplasia on core biopsy: Is excision always indicated?
Authors: Makarewich C. A. , Rosenkranz K. M. 
Published: February 2017

75 Background: Lobular neoplasia (LN) is a continuum of rare, noninvasive lesions of the breast including lobular carcinoma in situ and atypical lobular hyperplasia. Current management is controversial and often includes excisional biopsy in women diagnosed with LN on percutaneous core biopsy (PCB) to exclude an occult malignancy. This strategy is based on retrospective data in women undergoing selective excisions. We performed routine excision of all lesions diagnosed as LN in our institution in order to ascertain a more accurate assessment of pathologic upgrade. Methods: Retrospective review of all prospectively collected cases of LN treated in a single institution from 2007-2010. Excisional biopsies were performed in all cases of LN excepting one (patient declined). Histologic findings of excisional biopsies were reviewed to assess the rate of pathologic upgrade. Results: Of the 2,289 PCBs performed during the study period, LN was found in 23 cases (1.0%). Twenty two (0.96%) cases proceeded to excisional biopsy. On final pathology, malignancy was found in 4 patients (18%). Two of 22 (9%) women were upgraded to ductal carcinoma in situ (DCIS) (both intermediate grade with foci of <1mm and 4mm) and 2/22 (9%) women were diagnosed with invasive lobular carcinoma. Conclusions: While 18% of women in our series had upgraded pathology at the time of excisional biopsy, we support selective rather than routine excisional biopsy. One of the invasive diagnoses was an incidental finding unrelated to the microcalcifications for which biopsy was initially performed. In the second case of invasive disease, the upgraded lesion was a mass identified on MRI performed for surgical planning in a woman already diagnosed with breast cancer. In both cases of DCIS, the area of malignancy was small (<1mm and 4mm) and of uncertain clinical significance. Based on these findings, we do not recommend routine excision of all LN identified on PCB. Cases in which the lesion is associated with a radiographic mass and/or is identified in a breast with a synchronous malignancy do warrant excisional biopsy. Patients without these high risk features can be counseled on the risks of malignancy and given the option of observation with close follow up.
Serum calcitonin gene-related neuropeptide (CGRP) in patients with benign and malignant breast lesions: Correlation with mammographic breast density.
Authors: Papantoniou V. , Valsamaki P. , Fothiadaki A. , Archontaki A. , Skalistis V. , Marinopoulos S. , Liotsou T. , Karianos T. , Tsakmakli A. , Tsaroucha A. , Stipsanelli A. , Antsaklis A. 
Published: February 2017

78 Background: The aim of this study was to assess the variation of the serum neo-angiogenic neuropeptide CGRP in patients with benign and malignant breast lesions and to evaluate its possible correlation with mammographic findings. Methods: Our study included forty eight women with histologically confirmed breast lesions: mild epithelial hyperplasia (MEH): n=12, florid epithelial hyperplasia (FEH): n=5, atypical hyperplasia (AH): n=4, ductal carcinoma in situ (DCIS): n=5, mixed in situ with invasive ductal carcinoma (DCIS+IDC): n=9 and pure IDC: n=13. Serum CGRP levels were measured by RIA methods and compared among the various groups by Mann-Whitney test. Mammographic breasy density (BD%) was calculated using computer-assisted methods and was correlated with serum CGRP concentration by applying linear regression analysis. Results: Serum CGRP concentration (mean±SD: pg/mL) in the various groups, was: MEH: 96.8±22.5, FEH: 135.5±33.5, AH: 139±44.4, DCIS: 131.4±37.5, DCIS+IDC: 1167.5±927.5, pure IDC: 198±82. DCIS+IDC lesions presented statistically significantly higher serum CGRP levels (versus: MEH p<0.001, FEH p<0.001, AH p<0.001, DCIS p<0.001 and IDC p<0.001). Serum CGRP concentration presented statistically significant correlation with BD% (r=0.947, p<0.0001). Conclusions: Statistically increased serum CGRP concentration was determined in women with DCIS+IDC lesions. The significant correlation between serum CGRP levels and BD, enhances the suggestion that DCIS+IDC represents a distinct pathological entity, associated with an interactive mechanism between BD and serum CGRP expression. Therefore, serum CGRP levels could constitute a future useful preoperative index of the nature or type of suspicious mammographic lesions, in order to schedule the appropriate therapeutic treatment, and potentially propounds the perspective of adjunctive therapeutic administration of anti-CGRP peptides.
The ideal screening age for breast cancer in developing countries.
Authors: Al Ratroot H. , Wadaani H. , AbdelHadi M. S. A. 
Published: February 2017

79 Background: Due to the lack of structured breast cancer screening programs in developing countries early detection is generally based on international western criteria. This principle is not valid in many instances since women withdraw from voluntary involvement in such activities. In addition breast cancer in developing countries is characterized by younger age and advanced disease at the initial presentation. This review aims to identify the suitable screening age for women in developing countries in order to develop a reliable national structured screening programs. Methods: This retrospective study was undertaken at King Fahd Hospital of the University, eastern province of Saudi Arabia between 1984-2010. Medical records of patients diagnosed with from the outpatient department and hospital admission records was reviewed. It mainly focused on demographic data and the time of presentation. Radiological and histo-pathological records were also reviewed. Results: The total number of patients reviewed was 483. The majority of patients were within the reproductive age group. Considering the standard screening age is 40 years, patients are divided into two groups, group I included those below the age of 40 years accounting for 193 patients (40%), while group II above the age of 40 years accounting for 290 patients (60%). Patients in group I were mostly reassured and were mainly diagnosed initially using ultrasonography, while in group II mammography aided in diagnosis. Conclusions: Despite the undisputable concept that breast cancer has higher predilection for women above the age of 40 years, yet in developing countries, a substantial subset of affected younger women contradicts this concept. The need for breast cancer screening cannot be overemphasized, yet, international screening guidelines for breast cancer cannot be fully implemented in developing countries. Therefore, it is mandatory that screening programs should be tailored according to individual communities. Dropping the screening age by a decade may possibly increase the capture of early breast cancer and improve the outcome.
Use of a novel device to reduce positive margins for ductal carcinoma in situ.
Authors: Boolbol S. K. , Cocilovo C. , Tafra L. 
Published: February 2017

87 Background: The ability to obtain negative margins with a single surgical procedure remains a challenge, particularly in patients with ductal carcinoma in situ (DCIS). A novel device (MarginProbe, Dune Medical Devices, Inc.) is intended to provide surgeons with real-time, intraoperative detection of cancerous tissues at the margins of excised specimens. A study was performed to determine if there was a device-associated improvement in complete surgical resection (CSR) and therefore a decreased re-excision rate in patients with a DCIS component. Methods: 596 patients who were undergoing breast conservation using needle localization were randomized in a prospective, international, multicenter (n=21) study. Randomization occurred in the operating room, following standard of care lumpectomy, including palpation followed by indicated additional cavity resections. Device positive readings required additional resections of the cavity. Pathologists were blinded to study arm. A primary endpoint of this study was CSR, defined as the correct intraoperative identification and resection (if not skin or fascia) of all positive margins on the main lumpectomy specimen. Positive lumpectomy specimens were those having at least one margin having cancer ≤1mm from the surface. Successful CSR results in reduced positive margin rate after lumpectomy. Results: The improvement in CSR was significant for each diagnosis (p<0.0001). The decrease in candidates for reexcision due to failed CSR was significant for all pathology involving DCIS (p<0.0001). Overall results are presented in the table. Conclusions: Device use delivered significant improvement in CSR and therefore a significant decrease in reexcision rates for patients with DCIS. Further studies need to be conducted evaluating the use of the device on additional margins that the surgeon may resect or in the actual cavity. [Table: see text]
Surgical margins and the risk of local-regional recurrence (LRR) following mastectomy for early-stage breast cancer.
Authors: Childs S. K. , Chen Y. , Pochebit S. , Golshan M. , Duggan M. M. , Wong J. S. , Harris J. R. , Bellon J. R. 
Published: February 2017

95 Background: We sought to clarify the influence of a positive or close superficial or deep mastectomy margin on the risk of LRR. Methods: We reviewed the charts of 561 consecutive women who underwent mastectomy without radiation for newly diagnosed in situ or invasive breast cancer between 1998 and 2005. The study cohort consists of 167 of these women who had a positive or close (≤2 mm) superficial or deep surgical margin. LRR as the site of first recurrence (+/− simultaneous distant disease) and distant metastasis (DM) rates were calculated using the Kaplan-Meier method. The median age was 50 years. Forty-five (27%) had ductal carcinoma in situ (DCIS) only. Of the 122 women with invasive disease, 79% had T1, 18% T2, and 3% T3 tumors, and 25% had positive axillary nodes (range, 1-4; 68% 1 positive node). Twenty-nine (24%) of those with invasive disease had lymphovascular invasion. The superficial margin was positive in 61 (37%) and close in 69 (41%). The deep margin was positive in 28 (17%) and close in 51 (31%). Results: The median follow-up was 6.3 years (range, 1-12.4). The 5-year LRR rate was 5% (95% CI 2-10%) and the DM rate was 3% (95% CI 1-8%). Twelve patients had a LRR; this included the chest wall in 9 and the axilla in 4. Five of the 12 had positive nodes. Four of 92 (4%) with close margins had a LRR vs. 8/75 (11%) with positive margins (log-rank p=0.15). Of the 45 with pure DCIS, 1 (2%) had a LRR. Of those with invasive disease, LRR occurred in 1/28 (4%) who had invasive disease at (positive) or near (close) the superficial margin, 3/38 (8%) with DCIS at or near the superficial margin, 0/12 with invasive disease at or near the deep margin, and 1/12 (8%) with DCIS at or near the deep margin. Both margins were positive or close in 32/122 patients with invasive disease; 6 of these (19%) had a LRR. Conclusions: The risk of LRR in patients with a positive or close surgical margin after mastectomy is generally low. The benefit of post-mastectomy radiation in this population with otherwise favorable features is likely to be small. While there may be a higher risk of LRR in patients with disease at or close to both margins (likely representing extent of disease), numbers in these categories are small and these results should be interpreted with caution.