bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers and facilitators for clinical trial participation among diverse Asian patients with breast cancer.
Authors: Lee Guek Eng , Ow Mandy Y.L. , Lie Desiree , Dent Rebecca Alexandra
Published: February 2017

108

Background: Recruitment rates for breast cancer trials are low for racial/ethnic minorities. Little is known about factors influencing trial recruitment in Asian patients. Our aim is to examine the barriers and facilitators for participation in trials among multi-ethnic Asian women with breast cancer. Methods: We recruited a convenience sample from consecutive women seen at a National Cancer Centre. Two experienced bilingual (English and Chinese) moderators conducted focus groups to theme saturation. The question guide incorporated open-ended questions soliciting opinions about trial participation and knowledge. Women were first asked if they were willing, unwilling, or still open to participate in future trials. Sessions were audiotaped and transcribed. Transcripts were independently coded for emergent themes. Results: Sixteen of 103 women approached participated in five focus groups. Chinese, Malay and Indian participants aged 29 to 69 represented different cancer stages. Five had no prior knowledge of trials. We identified three major areas consisting of 24 minor themes for barriers and facilitators. Major themes fell into: 1) individual- or patient-related, 2) trial-related and and 3) sociocultural factors. When analysis was stratified by willingness to join trials, we found that women willing to join trials expressed themes representing facilitators (better test therapy, cost-effective profile, or trust in doctors and local systems). Women unwilling to participate expressed themes associated with barriers, while women still open to participation expressed themes representing both facilitators and barriers. Malay women were more likely to express themes related to ‘fatalism’ as a barrier. Conclusions: We found that facilitators and barriers to trial participation among Asian women were similar to those previously reported in Western women. Knowledge of trials is limited among women receiving breast cancer treatment. Unique sociocultural factors suggest that approaches customised to local and community beliefs are needed to improve trial participation in minority groups.
Secondary nonbreast malignancies (SNBM) after primary breast cancer (BC).
Authors: Habib Joyce Georges , Espirito Janet L. , Harrell Robyn K. , Turnwald Brian , O'Shaughnessy Joyce , Patt Debra A.
Published: February 2017

112

Background: BC survivors are at higher risk of developing SNBM due to treatment effects and shared behavioral and genetic factors. Associations between histologic subtypes of primary BC and secondary endometrial or ovarian cancer have been reported. Less is known about subtype-specific associations with other secondary solid tumors. We aimed to determine the prevalence of SNBM across US Oncology practices and what subtype-specific associations, if any, exist between primary BC and SNBM. Methods: We conducted a retrospective database analysis identifying BC patients (pts) diagnosed between 01/2007 and 05/2013. SNBM were ascertained from codified fields in pts electronic records. Age at BC diagnosis, BC stage, estrogen receptor (ER), progesterone receptor (PR), HER2 status, BMI and smoking history were collected. Chi-square tests were used to compare categorical variables. Logistic regression was used to predict likelihood of secondary malignancies in separate multivariate models. Results: 105,795 pts with stage 0-IV BC were identified. 2,237 (2.1%) were diagnosed with ≥ 1 SNBM. Mean age at diagnosis and follow-up were 59.5 and 2.6 years respectively. Pts with SNBM were more likely to have: older age, ≥ stage I, HER-2 negative disease, BMI ≥25 and past/current smoking history. SNBM were most commonly: Non-small cell lung cancer (NSCLC) (n=346), colorectal (CRC) (n=250), uterine (n=192), ovarian (n=130), thyroid (n=106) and kidney cancer (n=73). No associations were found between BC subtypes and ovarian, uterine, thyroid or NSCLC. Significant positive and negative associations between triple-negative breast cancer (TNBC) and secondary CRC and kidney cancer, respectively, were noted. In multivariate analysis, TNBC was predictive of secondary kidney cancer (OR 2.00, p=0.019). TNBC (OR 0.47, p=0.009), age ≤55 (OR 0.27, p<0.0001) and BMI ≤30 (OR 0.64 for BMI 25-30, p=0.019) were negative predictors of secondary CRC. Conclusions: Our study is the first to report direct and inverse associations between primary TNBC and secondary kidney and CRC, respectively. The short follow-up precludes treatment-related effects. Results may potentially be attributed to genetic, environmental or lifestyle factors and warrant further research.
Circulating tumor cells during and beyond maintenance therapy with SERM or aromatase inhibitors for decision making in long-term survivorship.
Authors: Pachmann Katharina , Rabenstein Carola , Camara Oumar , Rengsberger Matthias , Runnebaum Ingo B. , Pachmann Ulrich A.
Published: February 2017

119

Background: Although current guidelines still support 5 years of hormone blocking therapy after primary breast cancer due to earlier results showing no benefit of longer treatment, recent data have shown that longer treatment with tamoxifen can better reduce recurrence and death. However, side effects with this therapy can be considerable and compliance declines with time. We, here, report data on monitoring circulating epithelial tumor cells (CETC) beyond maintenance therapy showing that even if maintenance therapy with SERM or aromatase inhibitors had been effective in reducing tumor cells in blood, there can be a reincrease after the end of maintenance therapy and that this is highly correlated with relapse. Methods: 7.5ml of anti-coagulated blood was drawn before the start of chemotherapy, after each cycle and after the end of chemotherapy. Using a nondissipative approach with only red blood cell lysis the white blood cells including the tumor cells were stained with a fluorescent labelled anti-epithelial antibody, positive events counted using an automated image analysis microscope and calculated per volume blood. Results: 96 patients with nonmetastatic breat cancer were observed beyond maintenance treatment with hormone blocking therapy. Results on CETC were evaluable from 35 patients even after completion of therapy. Increasing cell numbers after the end of therapy were able to predict relapsing from long term relapse free survivors (p = 0.0001). Conclusions: In breast cancer, a debate has been reiinitated with respect to the length of maintenane treatment. Even if hormone blocking maintenance treatment is capable of reducing or even eliminating tumor cells circulating in peripheral blood and this is related to improved relapse free survival there may remain tumor cells in the body capable of re-growing and leading to late relapse. Monitoring of CETC in peripheral blood even after completion of maintenance therapy can early predict imminent relapse and help to decide whether to reinitiate hormone blocking therapy.
Uninsured utilization of the mobile mammography: 10-year analysis.
Authors: Riley Elizabeth Carloss , Rai Shesh , Pan Jainmin , Roland Lane , Barkley Laura , Mizuguchi Sarah
Published: February 2017

12

Background: Mobile Mammography Units (MMU) historically increase access breast cancer screening to uninsured patients. Our group previously reported insurance status predicts MMU repeat utilization (insured cohort most likely to repeat.) The purpose of this study is to examine the uninsured subset in multivariable analysis to understand the low repeat utilization by this group. Methods: From Jan 2001 to Dec 2010, 48,324 screening mammograms were performed in the largest county in KY. Of 21,587 unique subjects, 9,422 were uninsured (44%.) Demographic data was retrospectively reviewed to identify age, race/ethnicity, insurance status and location for each encounter. Utilization was defined as once or more than two times in a 10-year period. P-values were calculated using Chi-square test for comparison between the two groups. Odds ratio and its 95% confidence interval were provided. Logistics regression analysis is used to jointly model the effect of independent factors on repeat unitization of MMU. Results were declared significant at significance level of 5%. Results: Race, location, and age remain independent variables in likelihood of repeat utilization within a 10-year period (p value < .001.) The estimated OR are depicted in the table. We previously reported in the entire dataset (all insurance cohorts) and estimated OR of Whites (W) vs Blacks (B) of 0.897 (CI 0.843-0.955) and Hispanics (H) vs B 0.701 (CI 0.604-0.813.) Conclusions: Within the uninsured cohort, race and location remain independent predictors of repeat utilization of the MMU. However, the significance is weaker between W and B (p < .004 versus < .001) in the uninsured group than in the entire dataset which may suggest that insurance type becomes a stronger predictor of repeat utilization than race although further analysis will be necessary to confirm this trend.[Table: see text]
Comparing three methods for scoring late breast cosmesis in patients treated with lumpectomy and radiation therapy (RT).
Authors: Wong Andrew Thomas , Robertson-Parris Celina , Sura Sonal , White Carol , Chadha Manjeet
Published: February 2017

128

Background: For intact breast, the Harvard and LENTSOMA criteria are widely used to report late cosmesis. These scales require clinician’s interpretation and thus may be subject to variation between evaluators. Computerized tools exempt from evaluator bias are available to assess cosmesis. The objective of this study was to perform a comparative review of late breast cosmesis using the Harvard, LENTSOMA, and BCCT.core scales (Cardoso JS. et al; doi:10.1016/j.artmed.2007.02.007). Methods: A frontal bilateral breast photograph was used for analysis. Late cosmesis was scored with reference to the baseline breast appearance, ~ 1 year from RT distant from the acute treatment effects. Cosmesis was graded as excellent, good, fair, or poor using the Harvard scale. For LENTSOMA, only atrophy/retraction was assessed from the frontal breast photographs. The BCCT.core software was used as a validated tool for objectively scoring cosmesis and computes a score based on symmetry, color, and scar visibility. All outcomes were assessed by the same investigator (AW). Results: A total of 33 patients had 1-year baseline and follow up photographs. All were treated on a 3-week hypofractionated RT schedule, and none received chemotherapy. One hundred photographs, 1 to 5.7 years from end of RT, were scored. Late cosmesis among patients with good/excellent scores at 1-year remained unchanged by all 3 methods. Among patients graded as fair at 1-year, there was improvement in late comesis detected by Harvard and BCCT.core scoring. Late cosmesis by LENTSOMA criteria remained unchanged from baseline. Conclusions: Our experience suggests easy applicability of BCCT.core for scoring cosmesis in clinical practice. We observed no significant differences in cosmetic score by the methods used. However, these observations were made on a small cohort of patients and evaluation on a larger cohort is needed. The role of objective user-independent grading of cosmesis might be helpful in large comparative studies of clinical outcomes. [Table: see text]
Secondary primary cancers in male breast cancer survivors.
Authors: Shameem Raji , Hamid Muhammad S , Mavani Gaurang P , Singhal Nakul , Shani Dana , Sullivan Kevin M.
Published: February 2017

129

Background: Male Breast Cancer (MBC) survivors have an increased risk of developing secondary contralateral breast cancer. However, the risk of developing other solid tumors and hematological malignancies is not well understood. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to detect MBC cases diagnosed up to 12/31/2011. The Standardized Incidence Ratio (SIR) was calculated as the ratio of observed to expected cases of second primary malignancy based on incidence data in the general United States population. The latency exclusion period from the date of diagnosis was 5 years. We also investigated for any modifying effects such as radiation therapy, age at diagnosis, and latency period after initial diagnosis (5-10 years and >10 years) that may have increased the risk for secondary cancer. Results: A total of 1,239 men with an initial diagnosis of primary breast cancer were included in our analysis. Overall, there was an increased SIR of secondary solid tumors of the pharynx (SIR: 8.39, P<0.05), hypopharynx (SIR: 15.77, P<0.05), and brain (SIR: 4.40, p<0.05), and Non-Hodgkin Lymphoma (NHL) (SIR: 2.49, P<0.05), that was also seen in MBC cases that received radiation (24.1%), (SIR: 4.51, P<0.05). For MBC diagnoses in patients >40 years, there was an increased incidence for these malignancies and for “all solid tumors” (SIR: 1.30, P<0.05) as well. In the period ranging from 5-10 years after initial breast cancer diagnosis increased incidence for tumors of the pharynx (SIR: 8.95, P<0.05) and hypopharynx (SIR: 16.70, P<0.05) were seen. In contrast, there was no significant increased incidence of secondary cancers >10 years after initial diagnosis. Conclusions: MBC survivors are at increased risk for secondary malignancies of the pharynx, hypopharynx, brain, and NHL. Older age at diagnosis and radiation treatment appear to be risk factors. Risk of secondary tumors of the pharynx and hypopharynx is greatest 5-10 years after initial breast cancer diagnosis but optimal surveillance for MBC survivors requires further clarification.
Combining serum autoantibody measurements with traditional serum biomarkers for the detection of invasive breast cancer.
Authors: Henderson Meredith C. , Reese David Emery , Borman Sherri , Yeh Susan , Hollingsworth Alan
Published: February 2017

13

Background: The use of protein biomarkers for serum-based detection of invasive breast cancer has been problematic due in large part to intrinsic variability in the population as a whole. The Provista Biomarker Assay (PBA) has been shown previously to be highly sensitive across a wide spectrum of clinical signals. The detection of autoantibodies (AAb) holds great promise due to the inherent specificity these biomarkers provide. However, as a clinical-quality diagnostic, it is necessary to utilize a panel comprised of multiple autoantibodies, as individual sensitivity is general low. Our hypothesis was that combining serum protein and autoantibodies together in a panel would result in an increased ability to correctly identify breast cancer. Methods: To maximize clinical performance (sensitivity and specificity), we utilized the Meso Scale Discovery ELISA-based system to measure AAbs from patient sera. We analyzed 134 prospectively collected patient serum samples for a variety of autoantibody targets. These data, together with serum protein biomarker concentrations, produced an analytically robust test that is also highly specific. Results: Consistent with our hypothesis, the inclusion of autoantibodies with serum proteins in the Provista Biomarker Assay improved test specificity above that observed in serum protein biomarkers alone. Individual protein targets had limited ability to differentiate benign conditions from invasive breast cancer. However, factoring in autoantibody values resulted in improved overall accuracy to differentiate serum from benign and invasive breast cancer patients. Conclusions: In the novel approach of combining these two different classes of analytes, we exploit the specificity of AAbs while maintaining high sensitivity through the inclusion of more generalized cancer-associated protein biomarkers. The combination of these two approaches clearly offers unique performance benefits in the early detection of invasive breast cancer that is greater than either component alone.
Compliance with oral antiestrogens utilizing a bubble pack.
Authors: Riley Elizabeth Carloss , Dragun Anthony E. , McMasters Kelly , Scoggins Charles Raben , Quillo Amy R. , Rai Shesh , Wu Xiaoyong , Jain Dharamvir
Published: February 2017

132

Background: Adherence to endocrine therapy in breast cancer has been a long recognized problem despite efficacy to these drugs. Most of our knowledge of noncompliance has been largely observational and retrospective. Although multifactorial, extremes of age and race are risk factors for noncompliance. This report is an interim analysis of a well-designed study prospectively measuring compliance rates of “bubble” packaging of oral anti-estrogens Methods: A total of 88 patients were enrolled between August 2012 and April 2014. Out of 88 patients, 1 declined participation and 1 was deemed ineligible based on metastatic disease. Of the remaining 86, 53 continued participation and were included in this analysis. Demographic and clinical data were collected prospectively including age, race, insurance, duration of therapy, stage, and comorbidities. Duration of therapy was divided into 3 cohorts: early (less than 12 months), middle ( 12-36 months,) or late (37-60 months.) Comorbidities were defined as none, moderate (1-3) or significant (>3.) All patients received anti-estrogens in a “bubble”pack. All used bubble packs and missed dose diaries were returned at follow up appointments for review. Results: The majority of patients were white (77%)) and stage I/II (74%.) The overall compliance rate was 97%; however only 61% of enrolled patients were continued in the analysis. None of the variables examined race, age, insurance status and/ or stage had an impact on compliance. Only duration of therapy had a marginal effect on compliance (p value = 0.06.) The late cohort was least likely to be compliant at 89.53%, although only represented 9% of the included patients. Conclusions: The compliance rate of bubble packaging is higher than expected however should be interpreted with caution given the 39% withdrawal. Interestingly there was no difference in compliance rate among race, insurance status or age which contradicts our current knowledge on high risk groups. However duration of therapy did have a negative impact on compliance and may become increasingly important as duration of anti-estrogen therapy extends. However given the small number of patient in this cohort this will need to be confirmed at final analysis with larger involvement within this group. Clinical trial information: NCT01694225.
Factors influencing survival in inflammatory breast cancer.
Authors: Cupp Julie A. , Liu Diane , Shen Yu , Ueno Naoto T. , Alvarez Ricardo H. , Chavez-Mac Gregor Mariana , Woodward Wendy A. , Kogawa Takahiro , Babiera Gildy
Published: February 2017

136

Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer associated with poor prognosis, characterized by rapidly growing mass, skin changes, and regional adenopathy. The objective of this study was to determine if delay in treatment influenced survival in IBC patients. Methods: A prospective IBC database identified 93 women with stage III IBC who received care at MD Anderson from 2007 - 2012 and were retrospectively reviewed. All patients received neoadjuvant chemotherapy followed by surgery, unless progression of disease was noted, and postmastectomy radiation. Impact of time from onset of symptoms to chemotherapy or to surgery on overall survival (OS) and progression free survival (PFS) were evaluated after adjusting for the baseline covariates in the Cox model. Results: A majority of patients were white (77.4%) with an average age of 54 years. Average days from onset of symptoms to first chemo is 95 (range 16 – 387) and to surgery is 283 (range 184 – 585). Four patients had progression while on chemo. There were 14 deaths with median follow up of 2.6 years from diagnosis. In univariate analysis, delay in treatment, > 90 days from onset of symptoms to chemo, did not affect OS or PFS. Obtaining negative margins was statistically significant for OS and PFS measured from first chemo (p=0.005 and p=0.007). Positive HER-2 status was associated with longer PFS time from chemo (p=0.02, log-rank test) and from surgery (p=0.009). Positive progesterone receptor (PR) was found to be statistically significantly associated with longer OS time from chemo (p=0.01) and from surgery (p=0.03). Clinical and imaging response to chemo were associated with better OS (p=0.007 and p=0.005) and pathologic response was marginally associated with improved OS and PFS (p=0.07 and p=0.06), both measured from surgery. In multivariate Cox model, adjusting for PR or HER2, days from onset of symptoms to chemo or surgery did not have significant impact on OS or PFS. Conclusions: While traditionally delay diagnosis and treatment is considered one of the factors associated with poor prognosis, our study suggests otherwise. However, due to such rapid progression of disease, early diagnosis is still important in the overall management of patients diagnosed with IBC.
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

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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

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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

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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]
Does expression of estrogen receptor, progesterone receptor, and HER2 in atypical breast lesions predict a subsequent clinically significant event?
Authors: Tjoe Judy Angela , Neitzel Gary , Singh Maharaj , Last Brittany , Marx James , Kansra Sanjay
Published: February 2017

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Background: Atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) increase breast cancer risk 3-5 fold. Risk reduction strategies include intense radiographic surveillance, medical, or surgical prophylaxis, all with associated side effects. Thus, identifying predictors of future breast cancer associated with atypia would limit aggressive treatment to only those patients at highest risk for disease progression. Given that lifetime estrogen exposure is a risk factor for breast cancer, and human epidermal growth factor receptor-2 (HER2) gene amplification is linked to breast pathogenesis, we tested whether expression patterns of estrogen receptor (ER), progesterone receptor (PR), and HER2 at initial diagnosis of atypia predicted a subsequent clinically significant event (SCSE), defined as another occurrence of atypia, in situ, or invasive carcinoma. Methods: Patients with an initial diagnosis of ADH and/or ALH were retrospectively identified. 19 women who developed a SCSE (cases) were matched to 45 women with no SCSE for at least 5 years after the diagnosis of atypia (controls). Archived tissue from cases and controls were subjected to ER, PR, and HER2 immunohistochemistry. ER and PR were reported using Allred score (0 to 8). HER2 was reported as negative (0-1+), equivocal (2+) or positive (3+). Atypia with HER2 (2+) or (3+) scores were subject to SISH to confirm gene amplification. Results: There was no significant difference in expression of ER (mean Allred: cases = 7.26 ± 0.35; controls = 6.91 ± 0.43) or PR (mean Allred: cases = 6.95 ± 0.43; controls = 6.57 ± 0.34). >90% of both cases and controls were HER2 negative (0-1+). Longitudinal assessment of ER, PR, and HER2 in patients who developed a SCSE revealed that three of 19 cases presented with HER2 overexpression; however SISH analysis revealed no gene amplification. Interestingly, ER/PR expression decreased in three of seven patients with atypia who later developed an invasive malignancy. Conclusions: ER and PR expression do not predict a SCSE after an initial diagnosis of breast atypia. HER2 does not appear to be a useful marker for risk prediction of a SCSE, as HER2 overexpression was not identified in any of our cases.