bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of eribulin in patients (pts) with metastatic breast cancer (MBC): A pooled analysis by HER2 and ER status.
Authors: Kaufman Peter , Twelves Chris , Cortes Javier , Vahdat Linda T. , Olivo Martin , He Yi , Awada Ahmad 
Published: February 2017

137 Background: Eribulin (E) has been assessed in two phase 3, open-label trials in pts with locally recurrent or MBC progressing after an anthracycline (A) and taxane (T). E significantly increased overall survival (OS) compared with treatment of physician’s choice (TPC) in one study (EMBRACE) and there was a non-significant trend for improved OS with E vs capecitabine (cape) in the other (Study 301). We present an unplanned pooled analysis of these data. Methods: In the EMBRACE trial, women had received 2–5 lines of chemotherapy for advanced disease. In this ≥ 3rd line setting, pts were randomized 2:1 to E mesylate (1.4 mg/m2 iv on days 1 and 8 every 21 days) or TPC. In study 301, pts who had received 0-2 prior chemotherapies for advanced disease were randomized 1:1 to either E (as above) or cape (1.25 g/m2orally b.i.d. days 1–14 every 21 days). We analysed OS by 2-sided stratified log-rank tests and Cox regression in the overall intent-to-treat population and in the HER2-, triple negative (TNBC) and HER2+ subgroups. Results: 1,864 pts (median age 54 yrs) were included; most had been treated in the 2nd (31.5%) or 3rd line (32.7%) MBC settings. Overall, E provided significantly improved OS vs control; this benefit was also significant in HER2− and TNBC, but not HER2+ pts (Table). E improved progression-free survival overall (4.0 vs 3.4 months, HR = 0.90, 95%CI = 0.81, 0.997, p = 0.046), in HER2– (3.7 vs 3.0 months, HR = 0.84, 95%CI = 0.74, 0.95, p = 0.006) and TNBC pts (2.8 vs 2.6 months, HR = 0.78, 95%CI = 0.63, 0.96, p= 0.018). As reported before, the E safety profile was similar in the studies. Conclusions: E significantly improved OS vs standard therapies in MBC pts with HER2− and TNBC in this pooled analysis; in pts with HER2+ disease the difference did not reach statistical significance but numbers were smaller. Clinical trial information: NCT00337103 and NCT00388726. [Table: see text]
Health care professionals’ practices, perceptions, and awareness regarding breast self-examination.
Authors: Loh Kah Poh , Tan Eng Keong , Ogunneye Owolabi , Friderici Jennifer , Kleppel Reva , Stefan Mihaela , Stewart James A. 
Published: February 2017

14 Background: In 2009, the United States Preventive Services Task Force (USPSTF) published the revised guidelines for breast cancer screening which recommended against teaching breast self-examination (BSE).The objective of this study was to assess healthcare professionals' practices, perceptions and knowledge in BSE as well as their adherence to the newly revised USPSTF guideline for BSE. Methods: A cross-sectional survey study was carried out in five medical and gynecological practices affiliated with a large academic teaching hospital in western Massachusetts. The survey was sent to all attending- and resident-physicians, nurse practitioners (NPs), physician assistants (PAs), and registered nurses (RNs) working in these medical practices.The survey collected demographic data and inquired about practitioners’ awareness and perceptions of the 2009 USPSTF guidelines. Results: The survey completion rate was 50.7%. Fewer than half of respondents correctly identified the 2009 USPSTF guidelines recommendations for BSE (41.4%). However, among 35 respondents who stated they were aware of USPSTF guidelines, only 37.1% adhered to them. Overall, 70% (95% CI 61.3%, 79.1%) stated that they do teach patients to perform BSE. The most frequent reasons cited for teaching BSE were: “early detection of cancer” (48.0%), and to “empower women”, (37.0%). In univariable analyses, female practitioners were significantly more likely than male practitioners to report teaching BSE (OR 2.64, 95% CI 1.11, 6.29). Other characteristics which showed an association without reaching statistical significance were: ≥ 5 years of practice (OR 1.67, 95% CI 0.70, 3.98); non-physician practitioner (OR 3.5, 95% CI 0.82, 14.93); US Med School (OR 2.20, 95% CI 0.84, 5.75); ever detecting a lump in a patient (OR 2.95, 95% CI 0.80, 10.87), and belief that BSE reduces morbidity and mortality (OR 2.12, 95% CI 0.84, 5.37). Conclusions: Knowledge of, and adherence to, the 2009 USPSTF guidelines related to BSE are relatively low. Despite being aware of the guidelines, some health professionals still taught BSE. Greater efforts should be made to educate healthcare professionals about the 2009 USPSTF guidelines on BSE.
Clinical effects of prior anthracycline or taxane use on eribulin as first-line treatment for HER+/- locally recurrent or metastatic breast cancer (BC): Results from 2 phase 2, multicenter, single-arm studies.
Authors: Gluck Stefan , O'Shaughnessy Joyce , McIntyre Kristi , Schwartzberg Lee Steven , Wilks Sharon , Huggins-Puhalla Shannon Leigh , Berrak Erhan , Song James X. , Cox David , Vahdat Linda T. 
Published: February 2017

140 Background: Eribulin mesylate, a nontaxane microtubule dynamics inhibitor, has demonstrated an overall survival benefit relative to other commonly used agents in patients (pts) with at least 2 prior MBC cytotoxic therapies. Primary data presented from 2 phase 2 trials, Study 206 (eribulin in HER2- BC pts) and Study 208 (combination eribulin + trastuzumab [TRAS] in HER2+ BC pts), showed clinical activity and acceptable tolerability profiles as first-line cytotoxic therapy (tx). Here we present prespecified efficacy data for both trials based on prior anthracycline (A) and taxane (T) use. Methods: In both studies, pts received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 21-day cycle. Pts in Study 208 (HER2+) also received initial TRAS (8 mg/kg IV/Day 1), followed by 6 mg/kg/day 1 of each subsequent cycle. Objective response rate (ORR), progression-free survival (PFS), and tolerability were assessed. Results: In Study 206 (N=56), 48% and 46% received prior A and T, and in Study 208 (N=52), 21% and 44% received prior A and T, respectively. ORR, the primary endpoint, was similar in pts, regardless of prior A or T, except in pts w/o prior T in Study 208 whose ORR trended higher (table). Clinical benefit rate (CBR), PFS, and duration of response (DOR) were either similar or trended higher in pts w/o prior A or T. PFS was higher in HER2+ BC patients receiving eribulin + TRAS who had not received prior A or T compared with those who had. Grade (G) 3-5 adverse event rates were similar or lower in pts who had not received prior A or T. Conclusions: As first-line therapy, eribulin in HER2- BC pts and eribulin + TRAS in HER2+ BC pts were effective and well tolerated, regardless of prior A or T tx. However, in HER2+ BC pts receiving eribulin + TRAS, the lack of prior A or T tx may be a lead to longer median PFS. Clinical trial information: NCT01268150/NCT01269346. [Table: see text]
The effect of trastuzumab therapy on clinical benefit from fulvestrant treatment for metastatic estrogen receptor-positive breast cancer patients.
Authors: Charif Mahmoud , Lower Elyse E. , Kennedy Diane , Kumar Harriet , Khan Shugufta , Radhakrishnan Neetu , Zhang Xiaoting 
Published: February 2017

155 Background: Overexpression of HER2/neu is associated with tamoxifen resistance in breast cancer (Osborne CK et al. J Natl Canc Inst 2003; 95:353-361). However pts may present with both estrogen receptor (ER) and HER2/neu + tumors. The benefit of adding fulvestrant to trastuzumab is unclear. The objective of the study was to determine the effect of trastuzumab on fulvestrant therapy. Methods: This was an IRB approved record review of patients (pts) from three medical oncologists with biopsy-proven ER+ metastatic breast cancer treated with fulvestrant who also had their primary tumor tested for HER2/neu. Demographic data collected included age at diagnosis, type and stage of cancer, original and metastatic ER, progesterone receptor (PR), and HER-2/neu biomarkers, and site(s) of metastasis, and primary local and systemic treatment. All pts with HER-2/neu + primary tumors received trastuzumab. The duration of fulvestrant therapy was calculated. Time to clinical disease progression on fulvestrant was measured as a surrogate for duration of clinical benefit. Results: Eighty-five metastatic ER+ fulvestrant treated breast cancer pts with known primary tumor HER2/neu status were identified and the duration of therapy calculated. All eleven (13%) pts with documented HER2/neu + primary tumors received trastuzumab. The duration of therapy for HER2/neu + pts (772 (51-1911) days (median (range)) was longer than HER2/neu negative pts (360 (60-2,739) days, p=0.059). The median duration of fulvestrant therapy was 425 days. Pts with HER2/neu + tumors were more likely to be treated beyond the median fulvestrant therapy with an odds ratio of 6.2 (1.26 to 30.92 95% confidence interval, p=0.0249). Conclusions: Trastuzumab plus fulvestrant therapy was associated with a more prolonged clinical response than fulvestrant alone in pts with metastatic breast cancer. This synergism may be due to the effect of trastuzumab inhibiting the activation of transcriptional coactivator MED1, a recently discovered key crosstalk point between HER2/neu and ER signaling pathways in mediating endocrine resistance (Cancer Res 2012;72(21):5625;PLoS One 2013; 8:e70641).
A comparative effectiveness analysis of single-agent cytotoxics in triple-negative metastatic breast cancer patients.
Authors: Dranitsaris George , Glück Stefan , Faria Claudio , Cox David , Rugo Hope S. 
Published: February 2017

157 Background: There has been considerable progress in treatments for MBC. However, the identification of optimal cytotoxic agents in patients with triple negative disease (negative for hormone receptors, ER/PR and HER-2) remains a therapeutic challenge. A comparative effectiveness analysis of four cytotoxic agents was conducted in patients with TN MBC. Methods: We retrospectively identified 225 patients treated with single agent eribulin (E=47), capecitabine (C=69), gemcitabine (G=56) or vinorelbine (V=53) in 19 community oncology clinics across the US. Data collection included baseline patient characteristics, performance status, duration of current therapy, growth factor use and all dose limiting toxicities. Time to treatment failure (TTF) was measured from the first cycle of chemotherapy until disease progression, discontinuation due to toxicity, or death. TTF was then estimated using the Kaplan-Meier method and Cox proportional hazard modeling adjusted for clustering on the practice site. To control for selection bias that is inherent in observational studies, a propensity score weighted TTF analysis was also conducted. Results: Patients were comparable with respect to age, performance status, duration of disease free survival, presence of comorbidities and hemoglobin level prior to the start of chemotherapy. However, the median lines of therapy for use of C, G, V and E were 2nd, 3rd, 3rd, and 4th, respectively. The median duration of treatment was approximately 2 months with C, G, and E compared to 1.6 months with V. Using eribulin as the reference and adjusting for line of therapy and associated prognostic factors, the propensity score weighted Cox regression analysis did not identify statistically significant differences in TTF: C vs. E: HR = 1.15 (0.75 to 1.76), G vs. E: HR = 0.62 (0.34 to 1.13), V vs. E: HR = 1.0 (0.60 to 1.37). Conclusions: In patients with TN-MBC treated in a community oncology setting, eribulin was utilized in later lines than other agents. However, eribulin demonstrated at least comparable drug activity even when used in more heavily pretreated patients. These findings warrant further analyses in a larger population with an evaluation of biologic heterogeneity.
Preoperative MRI: Much ado about nothing?
Authors: Cate Sarah P. , Li Pamela , Rescigno John , Chadha Manjeet , Gillego Alyssa , Boolbol Susan K. 
Published: February 2017

16 Background: Preoperative MRI has been used to identify mammographically occult lesions and to determine extent of disease. However, the role of preoperative MRI in breast cancer remains controversial. We previously found that preoperative MRI does not increase total mastectomy (TM) rate. In this study we sought to identify a specific subgroup of patients in which preoperative MRI may be useful. Methods: In this IRB approved study, we conducted a retrospective review of 257 patients with breast cancer who underwent preoperative MRI from 2010 to 2012. We evaluated whether additional imaging and biopsies were recommended after MRI and whether it influenced the final surgical plan and decreased re-excision rate after partial mastectomy (PM). We collected data on several clinical factors and tested these for significant associations with both upgrading to TM and with the need for post-MRI imaging and biopsy using crosstab analysis and Fisher’s Exact test. Age as a continuous variable was also evaluated using binary logistic regression. Results: In our study cohort, 158 patients (62%) had additional imaging and 78 patients (30%) had additional biopsies recommended based on the MRI report. Of those biopsies prompted by MRI, 32 of them (39%) revealed cancer. The clinical significance, however, is subject to further study as only 3% of the 257 patients, eight upgraded to TM. We did not find any statistically significant differences in patients who were upgraded to TM by clinical factors such as age, menopausal status, mammographic breast density, ER/PR, HER2/neu status, or pathologic T stage; though there was a trend towards upgrade to TM in those who required additional imaging (p = 0.16). We found no clinical factors associated with the need for additional biopsies. Conclusions: We did not find a specific subgroup of patients in which preoperative MRI influenced management. Although preoperative MRI slightly increased the rate of TM, it does lead to numerous additional imaging studies and biopsies. Given these results, we are no longer using preoperative MRI routinely at our institution. Additional studies will be needed to determine strict indications for the use of MRI in the preoperative setting.
Expression of GHRH-R in primary and metastatic mammary carcinomas.
Authors: Block Norman L. , Nadji Mehrdad , Schally Andrew V. , Lara Jonathan F. , Michaelson Richard Alan , Ali Suhail M. , Leitzel Kim , Lipton Allan 
Published: February 2017

19 Background: In addition to its nominative function, as a neurohormone acting on the pituitary, Growth Hormone Releasing Hormone (GHRH) has been shown to modify the growth behavior of numerous cancers, including breast. GHRH is produced by tumor cells, acts in an autocrine/paracrine manner, and requires the presence of GHRH receptor (GHRH-R) on the tumor cells to exert its effects. As this work has been done predominantly on tumor cell lines and xenografts, we set out to examine the clinical analog. Methods: Matched primary and metachronous metastases from 50 breast cancers were included in this study of GHRH-R in breast cancer. Immunohistochemistry for GHRH-R (AbCam) was performed on paraffin sections and the staining results were assessed semi quantitatively from 0 (negative) to 3+ (strongly positive). A section from normal pituitary was use as positive control. Results: Forty-three of the primary breast cancers (86%) that ultimately relapsed or metastasized showed moderate to strong immunohistochemical expression of GHRH-R. Tumors from the metastatic foci also showed strong immunoreactivity in 78%, 71%, and 44% of liver, brain, and bone foci, respectively. The lower intensity of staining in bone samples may be due to the effect of the decalcification process routinely performed before staining. Whenever present, the non-neoplastic glands adjacent to breast tumors showed either negative or 1+ reaction for GHRH-R. The study population will be expanded to 100 patients, and the GHRH-R IHC results will be correlated with HER2, ER status, and clinical outcome. Conclusions: We conclude that the great majority of mammary carcinomas at primary and metastatic sites express GHRH-R. This finding could potentially serve as a basis for therapeutic approaches using peptide receptor antagonists. By receptor blockage using receptor antagonists, with minimal pharmacologic side effects, we have been able to control the growth in a number of tumor cell lines (HCC1806, MDAMB468, MDAMB435S, MCF7, T47D, HCC1937, BT474, and MX1s). Based on the presence of GHRH receptors in these clinical tumors, we conclude that clinical trials evaluating GHRH recpeptor antagonists are indicated.
Does age predict perceptions of recovery and long-term chest and upper body morbidity after postmastectomy breast reconstruction?
Authors: Johnson Donald Brooks , Lapin Brittany , Wang Chihsiung , Yao Katharine , Sisco Mark 
Published: February 2017

23 Background: Despite evidence that postmastectomy breast reconstruction (PMBR) yields important quality of life benefits, older women (≥ 65 years) rarely receive it. While the perception is that PMBR may result in greater physical morbidity in older women, the additive effects of age and PMBR on physical morbidity have not been studied. This study sought to assess long-term chest and upper body morbidity in older women who receive PMBR. Methods: Women with AJCC stage 0 to III breast cancer who underwent a mastectomy ± PMBR in 2006 to 2011 were surveyed; physical well-being was assessed using the BREAST-Q. Patients were grouped into (3) cohorts: younger (< 65 years) women who underwent PMBR, older women who underwent PMBR, and older women who underwent mastectomy alone. The groups were propensity matched (1:1) to control for differences. Data were analyzed using chi-square and t-tests. Results: 74 younger PMBR, 60 older PMBR, and 88 older unreconstructed mastectomy patients returned surveys (75.3% response rate). The median time from mastectomy to survey was 4.2 years. Younger women were more likely to undergo bilateral mastectomy than older women (54.3% vs. 28.4%, p < 0.001). 63.5% of women underwent implant-only reconstruction and 36.5% underwent autologous reconstruction; there were no significant differences in reconstruction type between age groups. Neither bilateral surgery nor reconstruction type affected BREAST-Q physical well-being scores. Among older women, PMBR was associated with lower mean physical well-being scores than mastectomy alone (79.4 vs. 87.4, p = 0.017, Cohen’s d = 0.56). However, there was no difference in physical well-being scores between older and younger PMBR patients (79.4 vs. 78.5, p = 0.614). Older PMBR patients perceived recovery from surgery as difficult more often than older unreconstructed patients (46% vs. 33%, p = 0.013), but less often than younger PMBR patients (46% vs. 61%, p = 0.036). Conclusions: Older women who undergo PMBR have more long-term chest and upper body morbidity than those who do not have PMBR. However, their morbidity from PMBR and perception of recovery from surgery is comparable to that of younger women. Older women should be counseled that while PMBR is associated with more long-term chest and upper body morbidity, this outcome is independent of age.
Who is ordering breast MRIs in newly diagnosed breast cancer patients?
Authors: Romanoff Anya , McMurray Matthew , Schmidt Hank , Tabrizian Parissa , Weltz Christina , Schwartzman Monica , Friedman Kathryn , Margolies Laurie , Port Elisa R. 
Published: February 2017

24 Background: Utilization of breast MRI has increased dramatically in recent years, and there is ongoing debate regarding the role of MRI in patients with breast cancer. Guidelines for MRI use in newly diagnosed breast cancer patients have not been established; therefore, provider ordering of MRI in this population is variable. We investigated patterns of MRI ordering by healthcare providers in the setting of newly diagnosed breast cancer and analyzed predictors of MRI utilization. Methods: All newly diagnosed breast cancer patients presenting for surgical management at a single tertiary care breast center from January 2011 through December 2013 were reviewed. Cases were evaluated for the use of preoperative MRI, and medical specialty of the ordering provider was determined. Patients who presented to a specialized breast center with MRI already completed were compared to those who had MRIs ordered by their treating breast surgeon. Results: A total of 423 women with newly diagnosed breast cancer underwent MRI during the study period. In this group, 253/423 patients (60%) presented to our institution with an MRI already completed. Of MRIs performed prior to presentation, 73% were ordered by a primary care provider, and 27% were ordered by a breast specialist seen previously. Race was a significant predictor of having an MRI before presentation to a breast center (64% of white patients, 41% of black patients, 25% of Asians, and 65% of Hispanic patients, p < .001). Women with commercial insurance were significantly more likely to have an MRI completed before presentation than those with Medicaid (62% versus 37%, p = .002). Age, family history of breast cancer, genetic testing, breast density, mode of diagnosis, and biopsy pathology were not significant factors in determining whether a patient underwent MRI prior to presentation to a breast surgeon. Conclusions: In our experience, the majority of MRIs performed in newly diagnosed patients with breast cancer were ordered by primary care providers as part of their patient’s initial workup. Patient race and insurance status were significant predictors of having an MRI ordered prior to seeing a breast specialist. Further research is needed to develop guidelines for breast MRI use in newly diagnosed cancer patients.
The 21-gene breast cancer assay in small (<1cm) tumors.
Authors: Russell Christy Ann , Stoppler Melissa Conrad , Rothney Megan , Sing Amy P. 
Published: February 2017

33 Background: Tumor size is a clinicopathologic factor often used in early stage breast cancer (EBC) management to estimate prognosis and make decisions about therapy. While in general, small tumors have a lower chance of recurring than large tumors, some patients with small tumors have poor outcomes. The 21-gene breast cancer assay (OncotypeDX) yields a Recurrence Score result that predicts the 10-yr risk of distant recurrence (DR) and the likelihood of chemotherapy (CT) benefit in patients (pts) with ER+ EBC. This study reviews the clinical evidence and experience of the 21-gene assay in subcentimeter (subCM) tumors and shows that the Recurrence Score is more reflective of the underlying tumor biology. Methods: A meta-analysis of Genomic Health validation and supportive studies reporting Recurrence Score result and tumor size was conducted in order to describe the distribution of Recurrence Score results. Results: There were 10 GHI-sponsored studies (7,094 pts) that presented Recurrence Score results as a function of tumor size. The studies varied in the recorded tumor sizes, ranging from < = 0.5 cm to > 5 cm. Four studies specifically examined the distribution of Recurrence Score results in subCM tumors and identified a total of 629 pts out of 2,912 pts (21.6%) that fit the size criteria of < 1cm. A broad distribution of score results was observed in subCM tumors in the four studies combined: 61% low, 25% int, 15% high. Conclusions: These results demonstrate that not all pts with subCM tumors have low risk disease, and that the 21-gene assay can help inform the risk of DR more precisely as well as predict the likelihood of CT benefit. Approximately 40% of pts had intermediate or high score results, suggesting an increased potential for DR and CT benefit. The clinical implications of this meta-analysis are that size doesn’t tell the whole story. There is underlying biology reflected in the Recurrence Score that can better inform the treatment decision for pts with ER+ EBC. [Table: see text]