bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors affecting lymphovascular invasion in node-positive breast cancer patients.
Authors: Cornwell L. B. , McMasters K. , Chagpar A. B. 
Published: February 2017

24 Background: Lymphatic and/or vascular invasion (LVI) is not uniformly reported in breast cancer tumors, and may be absent even in LN+ patients. The purpose of this study was to define factors associated with (a) the non-reporting of LVI, and (b) the finding of no LVI in LN+ patients. Methods: Data from 400 LN+ patients from a cohort of patients in a prospective multicenter study were reviewed. Institutional and clinicopathologic factors correlating with the reporting and finding of LVI were assessed using non-parametric statistical analysis. Results: Of the 400 LN+ patients in this cohort, LVI was not reported in 98 (24.5%) patients. Of the remaining 302 patients, LVI was reported as negative in 147 (48.7%). LVI was more often reported in later years (84.9% in 2001-2004 vs. 67.9% in 1997-2000, p<0.001). The reporting of LVI did not vary significantly by region, teaching affiliation, community size, or the surgeon’s proportion of breast practice or number of cases. Further, reporting of LVI was not associated with surgery type, patient age, number of positive nodes, size of largest metastasis, nor extracapsular extension. LVI was, however, more frequently reported in larger tumors (median tumor size 2.0 cm vs. 1.8 cm, p=0.030). Despite the finding that LVI was more frequently reported in later years, the proportion of patients found to have LVI did not vary by year (53.3% in 2001-2004 vs. 49.3% in 1997-2000, p=0.565), region, teaching affiliation, community size, or surgeon practice. LVI positivity was associated with younger age (median age 53 vs. 60, p=0.001), larger tumors (median size 2.5 vs. 1.8 cm, p<0.001), more positive lymph nodes (median 2.5 vs. 1, p<0.001), more macrometastases (58.7% vs. 36.5%, p=0.002), and more extracapsular extension (70.3% vs. 46.0%, p=0.001). Conclusions: Reporting of LVI has improved in recent years, and while the rate of LVI positivity has not changed in LN+ patients, it remains associated with poor prognostic factors in this cohort. Therefore, reporting of LVI should be encouraged as a standard part of synoptic pathology reports for breast cancer patients, regardless of lymph node status.
The INFORM HER2 Dual ISH assay compared with FISH to determine HER2 gene status in invasive breast carcinoma.
Authors: Loftin I. R. , McElhinny A. , Miller R. , Garcia C. , Bai I. , Ranger-Moore J. , Ostrem J. , Padilla M. , Grogan T. M. 
Published: February 2017

25 Background: The HER2 gene, located on chromosome 17 (Chr17), is amplified in 15-25% of patients with invasive breast carcinoma. Amplification and/or HER2 overexpression is associated with poor clinical outcome for these patients; however prognosis is improved if HER2 status indicates eligibility of patients for trastuzumab therapy. Thus, accurate diagnosis of HER2 status through a companion diagnostic is essential. Here we validated the INFORM HER2 Dual ISH Probe Cocktail (Dual ISH) assay as an alternative to FISH, the current gold standard for HER2 testing. The Dual ISH assay is fully automated and is scored using light microscopy. Methods: A multi-site method comparison and inter-laboratory reproducibility study were performed. 5 sites were used to compare Dual ISH results with FISH (Vysis PathVysion). 510 invasive breast carcinoma cases were stained at 3 clinical sites, FISH staining was performed at a fourth site (central laboratory). IHC status was determined at a fifth site (second central laboratory). In addition, 6 cases were evaluated for inter-site (3 sites), inter-reader (6 readers), inter-run (15 runs) and intra-run (duplicate slides) reproducibility. All assay steps were fully automated on a VENTANA BenchMark XT automated slide stainer, using a HER2 repeat-reduced, dinitrophenyl-labeled probe targeting the HER2 gene, detected with silver metallographic detection, and a digoxigenin-labeled Chr 17 probe, detected by an alkaline phosphatase-driven red chromogenic detection. HER2 and CHR17 signals were enumerated using conventional light microscopy allowing interpretation within the morphological context of the specimen. HER2 status was determined as the ratio of HER2/Chr17, where a ratio <2 is non-amplified and a ratio ≥2 is amplified. Results: The positive and negative agreement rates with FISH (95% CI) were 96% (92.6-97.9) and 92.3% (88.6-94.8), respectively. The HER2 Dual ISH assay also was highly reproducible in determining HER2/Chr17 ratio across sites, days, readers and runs. Conclusions: The fully automated INFORM HER2 Dual ISH assay is reproducible and concordant with the manual FISH assay in determining HER2 status in invasive breast carcinoma.
Risk of breast cancer (BC) relapse after 5 years of adjuvant tamoxifen (AT) in estrogen/progestrone-positive (ERP) patients (pts).
Authors: Barzi A. , Sisk B. A. , Yu C. , Budd G. T. , Kattan M. W. 
Published: February 2017

253 Background: Current standard of care for pts with ERP BC is 5 years of AT or aromatase inhibitors (AIs). Based on MA17 data, practitioners offer extended adjuvant therapy with AIs to post menopausal women. Extended therapy is costly and has side effects. Identifying pts with higher risk of relapse will allow practitioners to offer extended therapy to selected pts. Methods: Among 334 pts from the Cleveland Clinic BC surgery dataset, 38 had relapsed (local and systemic) and 39 had died of other causes. The 5 year absolute risk of late recurrence was calculated by cumulative incidence. We used a multivariable competing risks regression (CRR) analysis to determine the association of clinical parameters with late recurrence and treat death from other causes as competing risk. The predictor variables we tried to include are age at surgery, stage, pathology, progesterone receptor status and Charlson Comorbidity Index (CCI). Due to the limited number of recurrences, a parsimonious model with 3 predictors was desired. The model with the highest discrimination accuracy (quantified by Concordance index (CI)) selected as the basis of the final nomogram (ng). The ng was internally validated using ten fold cross-validation. The calibration of the ng prediction was checked visually by plotting the ng predicted risk of 5 year recurrence against the observed cumulative incidence from the data. Results: The 5-year risk of late recurrence or death from other causes were 0.066 (0.039 – 0.093) or 0.050 (0.026 – 0.073) respectively. The model that included age (<=60 vs > 60), stage (I vs others) and CCI had the highest discrimination (CI = 0.551), on which a final ng was constructed for predicting the 5-year probabilities of late recurrence. In our previous work we showed that CI in Adjuvnat Online (AO) is 0.569. Our calibration curve after ten-fold cross-validation looks comparable to AO model. Conclusions: We built and internally validated a ng for predicting the absolute probability of late recurrence for pts who completed five-year AT. Given the small size of our data set and the low number of recurrences our ng has fair discrimination and good calibration; however we were unable to outperform AO.
An algorithm for screening and treatment of breast cancer-related lymphedema.
Authors: Lopez Penha T. R. , Heuts E. M. , Tuinder S. , van der Hulst R. , von Meyenfeldt M. F. 
Published: February 2017

256 Background: Currently, there is no clear-cut regimen for the treatment of breast cancer related lymphedema. There is evidence advocating both conservative and micro surgical therapy, with treatment effectiveness being dependent on the lymphedema stage. We propose a multidisciplinary screening program with the aim of preventing breast cancer related lymphedema progression and ensure disease regression by early identification and treatment initiation. This approach would ultimately reduce the negative functional, psychosocial and cosmetic consequences resulting from (chronic) lymphedema. Methods: All women with early stage breast cancer are included in this screening program. We use preoperative and sequential postoperative bilateral upper limb circumference measurements and patient perception to identify lymphedema. A difference of > 2cm between post-operative and baseline circumference and patient perception of (refractory) swelling constitutes a diagnosis of lymphedema. Upon lymphedema diagnosis, patients are referred to a lymph therapist for initiation of conservative therapy in the form of complex decongestive physiotherapy. Therapy effect is evaluated after 1 month. In case of unsatisfactory symptom or limb circumference reduction, the patient is considered for surgical treatment. A plastic surgeon evaluates the possibility of microsurgical lymph vessel repair in the form of lymphatic-venous anastomoses or lymphatic-venous-lymphatic anastomoses. This minimal invasive surgery can improve lymph flow in the affected limb. If despite this, symptom improvement and patient satisfaction remains minimal, autologous lymph node transplantation is considered. Results: The aimed outcome parameters are 1) limb circumference reduction, 2) perceived symptom improvement: (refractory) swelling, 3) quality of life improvement, 4) limb range of motion improvement, 5) strength and sensory improvement, 6) restoration/improvement of lymph flow visualized by lymphoscintigraphy. Conclusions: A structured approach for a multidisciplinary treatment of breast cancer related lymphedema is proposed to reduce the negative functional, psychosocial and cosmetic consequences resulting from (chronic) lymphedema.
A study of atherosclerosis in patients after radiation for early breast cancer.
Authors: Kirtani V. G. , Chang M. , Dobrescu A. M. , Zeldis S. , Haas J. A. , Hindenburg A. A. 
Published: February 2017

260 Background: Radiation therapy (RT) is widely used as part of curative treatment of breast cancer. However, older studies have shown increased cardiac morbidity and mortality from breast RT. A screening method is needed to detect early cardiac damage in this population. Recent data have shown that Electron beam computed tomography (EBCT) can detect early atherosclerosis in coronary arteries by identifying the amount of calcification in the coronaries. In our study we employed this tool to detect occult atherosclerosis caused by breast RT. Methods: We evaluated 20 asymptomatic patients, less than 60 years of age, treated with RT at least 5 years prior to enrollment. Nine received RT to the left and 11 to the right hemithorax. Average interval between RT and CT was 7.7 years (5-14). All patients were treated with external beam RT using tangential technique. The breast was treated to a dose of 4500-5040 cGy and the tumor bed was boosted to a total dose of 6000-6600 cGy. All patients underwent EBCT to compute the volumetric and agatston calcium scores in the coronary arteries and the aorta. Results: Of the 11 patients who had RT to right hemithorax, 8 had calcium score of 0, 2 had very minimally elevated scores and 1 had significantly elevated score (patient 19, interval -14 years). Of the 9 patients who had RT to left hemithorax, 7 had calcium score of 0. None had significantly elevated scores. In the aorta, 11 patients had score of 0 and 8 had minimally elevated scores. Conclusions: Occult atherosclerosis was not detected using EBCT calcium scores in coronaries and aorta in a significant number of patients treated with RT for breast cancer. However, the study is limited by a small sample size. [Table: see text]
PTEN expression in Palestinian women with breast cancer, particularly in triple-negative subtype.
Authors: Khatib A. A. , AL Abed M. N. 
Published: February 2017

27 Background: According to data from the Palestinian Ministry of Health, breast cancer is the most common malignancy affecting Palestinian women, being 30% of all cancers affecting female patients, 60% of them present with metastasis, very few studies were conducted to explore characteristics of this cancer in this population. Triple-negative breast cancer (TNBC) has distinct clinical and pathologic features. The fact that this type is more aggressive despite lacking the expression of growth promotion receptors, suggest other players, as defect in tumor suppressors such as PTEN gene. To our knowledge this is the first study in English literature correlating TNBC to loss of PTEN protein expression. The aim of this study is to establish data about the clinicopathological characteristics of breast cancer in Palestinian women, and to study the status of PTEN protein expression by immunohistochemistry in breast cancer and specifically in TNBC. Methods: 100 confirmed cases of breast cancer, were collected from different pathology centers, clinicopathological data; age, grade, stage for each case were specified. Each case was evaluated for the expression of hormone receptors, Her-2 status, and for PTEN protein expression by immunohistochemistry (IHC) to see if a certain pattern is noted. Results: Out of the 100 cases, the mean age at presentation was 53.3 years, 69.84% of the cases presented with advanced stage and 53% were high grade, 58% were ER positive and 46% were PR positive. HER-2 positive breast cancer were 26%. 30% of all breast cancer cases were TNBC subtype. Loss of PTEN expression was seen in 44% of cases. 60% of TNBC cases lost PTEN expression, which was statistically significant (p + 0.035), no significant correlation between PTEN loss and ER, PR, HER-2, grade or stage. Conclusions: Palestinian women have high incidence of TNBC in comparison to White population, and presented with high grade, and advanced stage tumors. There is a significant correlation between PTEN loss and TNBC that needs more research and study.
Relationship between taxane-induced neuropathy and clinical outcomes after adjuvant chemotherapy.
Authors: Schneider B. P. , Wang M. , Stearns V. , Martino S. , Jones V. E. , Perez E. A. , Saphner T. J. , Wolff A. C. , Sledge G. W. , Wood W. , Davidson N. E. , Sparano J. A. 
Published: February 2017

270 Background: Neuropathy is a common and potentially enduring and disabling complication of adjuvant taxane therapy. Recent studies have identified candidate host single nucleotide polymorphisms (SNPs) associated with taxane-induced neuropathy (Schneider et al. ASCO 2011, abstr. 1000). We therefore sought to determine whether neuropathy was associated with breast cancer recurrence. Methods: This study included 4,950 eligible women with axillary lymph node positive or high-risk node-negative breast cancer who received up to 4 cycles of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks, followed by either: (1) paclitaxel 175 mg/m2 every 3 weeks x 4 (P3), (2) paclitaxel 80 mg/m2 weekly x 12 (P1), (3) docetaxel 100 mg/m2 every 3 weeks x 4 (D3), or (4) docetaxel 35 mg/m2 weekly x 12 (D1). Chemotherapy doses were based on actual body weight. Cox proportional hazards model were used to determine the relationship between neuropathy and disease free survival (DFS) and overall survival (OS) treating neuropathy status as a time dependent covariate and using a landmark analysis. Results: Of 4,702 patients who received at least 1 taxane dose, grade 2-4 neuropathy developed in 20%, 27%, 16%, and 16% in the P3, P1, D3, and D1 arms, respectively. In a model including age, tumor size, nodal status, treatment arm, neuropathy, and the neuropathy- treatment interaction, there was no relationship between neuropathy and DFS and OS in the entire population, for any of the individual treatment arms, or for any breast cancer subtypes, whether analyzed as a time-dependent covariate or using a landmark analysis. Baseline covariates associated with an increase rate of neuropathy included black race (25% vs. 19% grade 2-4, p=0.02) and obesity (21% vs. 19%, p=0.04), but not age. Conclusions: There was no association between taxane-induced neuropathy and DFS or OS in patients treated with contemporary AC-taxane therapy, including weekly paclitaxel. These findings show that taxane-induced neuropathy is not associated with outcome, thus suggesting that validation of SNPs predictive of neuropathy may be useful in identifying patients at higher risk for neuropathy but not taxane benefit and thereby improve therapeutic individualization.
Effect of denosumab versus zoledronic acid on health-related quality of life in patients with metastatic breast cancer.
Authors: Fallowfield L. , Patrick D. , Body J. , Lipton A. , Tonkin K. S. , Qian Y. , Jiang Q. , Braun A. H. , Dansey R. D. , Chung K. 
Published: February 2017

272 Background: Patients with breast cancer and bone metastases often experience skeletal-related events (SREs) and pain, which can impact health-related quality of life (HRQoL). Denosumab is superior to zoledronic acid (ZA) in preventing SREs and more effective in delaying moderate or severe pain in patients with advanced breast cancer. We now describe the effect of denosumab or ZA treatment on HRQoL in these patients. Methods: Patients enrolled in this double-blind, double-dummy study were randomized to receive denosumab (120 mg SC) or ZA (4 mg IV) every 4 weeks. Patients completed the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at baseline (BL), day 8, and each monthly visit to assess overall HRQoL. Higher scores (range 0 to 108) reflect a better HRQoL. Changes in HRQoL were summarized through month 18, when 30% of patients had died or dropped out due to disease progression or withdrawal of consent. Increases or decreases of ≥ 5 points in the FACT-G total score were considered clinically meaningful. Pain was evaluated by the Brief Pain Inventory–Short Form (BPI-SF). HRQoL was assessed in subgroups with no/mild pain or moderate/severe pain at BL. Results: The BL mean (SD) FACT-G score was similar for denosumab (n = 956) 72.7 (16.4) and ZA (n = 952) 73.6 (16.5) groups and increased from BL to month18 for both groups reflecting improved HRQoL. An average of 3.2% more (range 0.9% to 6.8%) denosumab-treated patients than ZA-treated patients experienced a ≥ 5-point increase in HRQoL from months 1 to 18. Fewer denosumab than ZA-treated patients reported a ≥ 5-point decrease in HRQoL (average 2.7% fewer; range 0.6% to 5.8%). Among patients with no/mild pain at BL, an average of 4.1% more (range -0.6% to 9.3%) denosumab-treated patients had a ≥ 5-point increase in FACT-G score from month 4 to 18. In this same subgroup, fewer denosumab-treated patients had a ≥ 5-point decrease in HRQoL over 18 months (average 2.4% fewer; range -4.4% to 6.3%). Similar patterns in FACT-G scores were noted for the subgroup with moderate/severe pain at BL. Conclusions: In patients with advanced breast cancer, a greater proportion treated with denosumab than ZA had a meaningful improvement in HRQoL regardless of BL pain level.
Antiestrogenic effects of the natural fetal estrogen estetrol (E4) in women with estrogen-receptor-positive early breast cancer.
Authors: Singer C. F. , Natter C. , Steurer S. , Moinfar F. , Visser M. , Appels N. , Kubista E. , Coelingh Bennink H. 
Published: February 2017

280 Background: Estetrol (E4) is a fetal estrogen which exerts estrogenic effects on vaginal epithelium, hot flushes and bone, but has estrogen-antagonistic effects on breast cancer cell lines in vitro and in the rat DMBA model. Therefore E4 may be suitable for Hormone Replacement Therapy (HRT) in women with breast cancer including women treated with aromatase inhibitors. Methods: We have investigated the effect of 14 days pre-operative treatment with 20 mg E4 per day on proliferation, apoptosis, ER-receptors and sex steroid levels in a prospective, randomised, double-blind, placebo-controlled, neo-adjuvant study in 15 pre- and 15 postmenopausal women with estrogen-receptor positive early breast cancer. Results: Estetrol induced a significant increase of SHBG, a significant decrease of FSH in postmenopausal women and no increase of gonadotrophins in premenopausal women. Estetrol had no effect on Ki67 expression and on apoptosis-related Bax and Bcl-2, but the apoptosis index in tumor tissue increased significantly. Systemic IGF-1 levels decreased significantly. Surprisingly the intratumoral epithelial ER-alpha expression decreased significantly, whereas the ER-beta expression showed a trend to increase. Conclusions: This data show that E4 has estrogenic endocrine effects. The data support the hypothesis that E4, may be suitable and safe for HRT in women with spontaneous or induced menopausal symptoms, since apoptosis increases, IGF-1 decreases and no unfavourable effects are observed on Ki67, Bax and Bcl-2. The decrease of ER-alpha and the increase of ER-beta suggest a mechanism of action, explaining why the natural fetal estrogen E4 has estrogen-antagonistic effects on breast cancer tissue.
Safety of adjuvant trastuzumab (T) in elderly patients with breast cancer.
Authors: Militello L. , Carli P. , Spazzapan S. , Lestuzzi C. , Miolo G. , Scalone S. , Veronesi A. , Crivellari D. 
Published: February 2017

282 Background: T is a mainstay in adjuvant therapy for HER2+ breast cancer (BC) patients (pts). Safety and efficacy of T in elderly patients are largely unknown. In HERA trial, NSABP B-31, NCCTG N9831 only 16% of pts were older than 60 years. Risk factors for T related cardiotoxicity are age (>50 y/o), hypertension, baseline LVEF (left ventricular ejection fraction <55%), previous antracycline therapy and BMI. Methods: Charts of pts >65 y/o with early HER2+ BC treated with T as adjuvant or neoadjuvant therapy at our institution were retrospectively reviewed. Primary endpoint was the evaluation of T cardiac toxicity and safety. Results: 22 elderly out of 172 pts (12%) were identified: 19 pts were treated only with surgery and adjuvant chemotherapy with concomitant or sequential T, 3 more pts also received neoadjuvant chemotherapy concomitant with T. According to Balducci’s criteria, fit, vulnerable and frail pts were 20, 2, 0 respectively. Median age was 69 y/o (range 65-76). Hormonal status was negative in 10/22 (45%). 21/22 were histologic grade 3. Median follow-up was 33 months. Baseline comorbidities were the following: hypertension (G2-3) in 17 pts, diabetes mellitus in 1, supra/infraventricular arrhythmia (G1-2) in 3 and 1 pts. Antracyclines were administered in 16 pts (liposomal-doxorubicin in 5 pts), a sequential taxane-regimen was used in 3 more pts. Neoadjuvant weekly Paclitaxel and concomitant T was used in 3 pts. Median basal LVEF was 65% (range 59-74%). 2 pts developed an asymptomatic 10% LVEF drop from baseline (left ventricular systolic dysfunction G1) during T treatment. Known cardiac risk factors were hypertension in 1 pt and previous antracycline based chemotherapy in both. They recovered within 9 months. One minor adverse event was atrial fibrillation (G2) during T treatment. Conclusions: T was well tolerated in elderly pts. More data are needed in order to understand the correlations between T related toxicity and cardiovascular risk factors. Long term safety of T treatment should verify the reversibility of cardiac T related toxicity on elderly pts.