bluuebunny/crossref_metadata_2025 huggingface dataset:
Adherence to hormone treatment for breast cancer and beliefs about treatment and screening.
Authors: Lin Jenny J , Joseph Kathie-Ann P. , Fei Kezhen , Franco Rebeca , Bickell Nina
Published: March 2020

e11004

Background: Beliefs about medications, more than knowledge, have been found to affect medication adherence. For breast cancer patients, at least 5 years of daily adjuvant hormonal therapy (HT) improves survival but it is often difficult for women to sustain therapy. Qualitative studies suggest women take HT to prevent breast cancer recurrence. We sought to assess whether beliefs about HT and screening were associated with ongoing HT adherence. Methods: Patients with a new early-stage breast cancer enrolled in an IRB-approved RCT to reduce disparities in care in New York City were telephone surveyed 6 months after their surgical treatment for breast cancer to assess knowledge, attitudes and beliefs about breast cancer, its treatment and prevention. Adherence was defined as a positive response to “are you now taking hormonal therapy (e.g., tamoxifen, arimidex)?” Beliefs about HT and mammogram screening were assessed. Bivariate analyses were conducted with t tests, chi square or Wilcoxon rank sum tests; multivariate analysis used a stepwise logistic regression. Results: Of 333 enrolled women, 233 were recommended to take HT. Of these, 187 (80%) women were prescribed HT and 172 (92%) were still adherent 6 months after surgery. Fifty-three percent of women were bothered by side effects but all were adherent; however, of the 15 women who stopped HT, 6 (40%) stopped due to side effects. Sixteen percent of women expressed difficulty paying for HT but all were adherent. Patients adherent to HT had stronger beliefs in both HT as treatment and prevention and in the importance of regular mammograms to stay healthy. A multivariate model including race, insurance, HT knowledge and beliefs found that only beliefs about HT and mammogram screening were associated with adherence (belief about HT: OR=1.1; 95%CI: 1.03-1.11; belief about mammogram: OR=1.55; 95% CI: 1.06-2.27) [model c=.84; p<0.0001]. Conclusions: Ongoing HT adherence is related to beliefs about both treatment and screening.Adherence is not related to HT knowledge, side effects, cost, insurance or patient race. Understanding patients’ beliefs about screening and treatment may help physicians enable women to adhere to long-term therapy.
Variations of the ER, PR, and HER2 expression status according to operation day in breast cancer patients.
Authors: Arik Zafer , Aksoy Sercan , Sendur Mehmet Ali Nahit , Yaman Sebnem , Altundag Kadri
Published: March 2020

e11009

Background: Estrogen receptor (ER), progesteron receptor (PR) and HER-2 are prognostic and predictive markers in the management of breast cancer treatment. Delay in fixation of the specimens may reduce the ability to detect breast cancer biomarkers and resulting in false negative immunhistochemical results. Handling of specimens from operation rooms to pathology laboratories may delay sometimes, especially Fridays. We hypothesized that ER, PR and HER-2 expression status may change according to the day of surgical procedure. Methods: Patients who operated between 2005 and 2010 for breast cancer in our Hospital were analyzed retrospectively. Consecutive 462 patients who had breast conserving surgery and modified radical mastectomy were included into the study. Patient’s demographics data and tumor characteristics and surgical procedure day were obtained from medical charts. Results: The mean age of the study population was 50±11 years. There were not differences between the T, N, M stage and age of patients according to operation day. ER, PR, HER-2 expressions were similar in Monday, Tuesday, Wednesday and Thursday. So we grouped the patients operated on Friday and others. Among the patients, 121 (26%) were operated on Friday. ER and PR negativity was higher on Friday procedures than the other weekdays (40% vs 23.2%; p=0.008 and 35.7% vs 27.9%; p=0.08, respectively). HER-2 positivity on Friday was significantly higher than the other weekdays (41.9% versus 23.4%; P=0.005). Conclusions: Cold ischemic time is the interval between removal of the tissue and placement in the tissue fixative. ER and PR are thermolabile proteins whose levels of expression are altered by prolonged cold ischemic time. Studies have shown delays in handling of breast cancer tissues affect biomarkers positivity and some tumors were classified falsely as negative. Specimens obtained on Friday may have more delaying for handling; therefore may have more hormon receptor negative results. In our study we have shown that ER negativity and HER-2 positivity are significantly higher on patients who were operated on Friday. Our study showed that handling of the specimen to the pathology laboratories is crucial and affect the treatment decisions.
Young patients with breast cancer (< 35 years): Single-institution study of 194 patients from India.
Authors: Mohanti B. K , Raina Vinod , Gogia Ajay , Deo S. V. S , Shukla N. K
Published: March 2020

e11013

Background: Breast cancer in young women ( < 35 years) is uncommon and accounts for 1-2 % of all breast cancer in the West .There is paucity of data on young breast cancer from India. The aim of our study was to assess clinical and pathological parameters and outcome in young breast cancer patients. Methods: Annually we register approximately 350 new cases of breast cancer of whom young patients constitute a small fraction. This analysis was carried out in 194 patients with aged 35 years or less, who were registered in our clinic between 2000-2009, this constituted about 5.5 % of all new cases. Patients records were analysed from computer database using ICD code (C-50) Results: The median age was 31 years (range 21-35). The median duration of symptoms was 11.8 months (range 0.5-40). Breast lump was the commonest (93%) presenting symptom (left >right side). Ninety percent of patients were married and median age at first child birth was 23 years. Positive family history was elicited in 8 patients, and 3 patients presented with synchronous malignancy. The TNM (7th edition) stage distribution was stage I was 3 %, stage II- 20%, stage III- 55%, and stage IV- 22%. The median clinical tumour size was 5.9 cm. Modified Radical mastectomy was the commonest surgical procedure and this was done in 81 % of cases. The histopathological analysis showed 94% had infiltrating ductal carcinoma. Sixty percent of tumours were high grade and 56% had pathological node positive disease. ER/PR status and Her2 Neu status was available in 65% and 50% respectively. Out of these patients ER and her2neu positivity was 40% and 37% respectively. Triple negative breast cancer (TNBC) constituted 31%. A combination of anthracyclines and taxanes were used in the vast majority of patients and herceptin was used only in 5 %. With a median follow up of 30 months, three years event free (EFS) and overall survival (OS) was 50% and 60%. Higher Nodal stage, tumour size (>5 c.m ), negative ER/PR status and visceral metastasis at baseline predicted poor outcome. Conclusions: Young women constituted 5.5% cases with higher proportion of triple negativity, this is higher than the western population reflecting younger age of our population of breast cancer in general with a resultant poorer outcome.
Genetic variants of kinases suppressors of ras (KSR1) to predict survival in patients with ER-alpha positive metastatic breast cancer.
Authors: Zhang Wu , Benhaim Leonor , Yang Dongyun , Gerger Armin , Bohanes Pierre Oliver , Páez David , Loupakis Fotios , Wakatsuki Takeru , Labonte Melissa Janae , Ning Yan , El-Khoueiry Rita , Zhang Hua , Stebbing Justin , Giamas Georgios , Lenz Heinz-Josef
Published: March 2020

e11018

Background: In addition to its activating role of MAPK pathway, the protein kinase suppressor of ras 1 (KSR1) has been identified as a novel modulator of estrogen receptor alpha (ERα), as silencing of KSR1 in ERα+ breast cancer (BC) cells lines resulted in dowregulation of ERα transcriptional activity in the presence of oestradiol. Our previously data revealed the existence of single nucleotide polymorphisms (SNPs) in EGFR and ERα pathway genes that may predict clinical outcome in ERα positive metastatic BC (mBC) patients. With respect to those findings we aimed to evaluate the clinical implication of KSR1 SNPs on survival in patients with primary ERα+ mBC treated with tamoxifen. Methods: Tumoral DNA was obtained from 222 patients treated with tamoxifen withERα+ invasive BC who had undergone surgery between 1981 and 2003 (median age 56 [28-90]). Three relevant KSR1 SNPs were selected based on public literature resources and databases, including 2 SNPs localised in the regulating 3’untranslated region (rs224190, rs 1075952) and 1 non-synonymous SNP localised in the coding exon 7 region (rs2293180). All SNP were analysed using DNA sequencing with OS and DFS as primary endpoint. Results: The overall median follow-up was 6.4 years.In univariate analysis the rs2241906 SNP was significantly associated with DFS and OS and patients with the TT genotypedemonstrated shorter DFS (2.1 vs. 7.1 months, p=0.005) and OS ( 2.6 vs. 8.4 months p=0.002) than patients with the x/C genotypes. The associations remained significant in the multivariate analysis adjusting age, lymph node status and HER2 status (HR (95%CI): 4.81 (2.00-11.59) and 5.74 (2.29-14.43), for DFS and OS, respectively). The same significant correlation was retrieved with the SNP rs1075952 in linkage disequilibrium with rs2241906 that was used as a control. No relationship was shown between rs2293180 and survival. Conclusions: Our findings demonstrated that KSR1 polymorphisms could arise as a potential marker to predict survival in patients with mBC treated with tamoxifen. The putative role of KSR1 as a modulator of ERα activity could functionally explain our results yielding insight for further studies.
Prognostic relevance of partial hormone receptor expression in stage I breast cancer.
Authors: Zwenger Ariel , Leone Julieta , Iturbe Julian , Perez Verdera Palmira , Leone Jose Pablo , Leone Bernardo Amadeo , Vallejo Carlos Teodoro
Published: March 2020

e11021

Background: Patients whose tumors express only one hormone receptor (1HR) are usually considered hormone-sensitive regarding treatment decisions. However, certain retrospective analyses suggest that patients bearing ER+/PR- or ER-/PR+ tumors may have worse outcomes than those with ER+/PR+ (HR) phenotype. The aim of this study was to correlate partial expression of hormone receptors (ER+/PR- or ER-/PR+) with several well known prognostic factors and their possible influence on the incidence of local and distant failure, relapse free survival (RFS) and overall survival (OS) in women with early breast cancer treated at GOCS institutions. Methods: We evaluated 327 patients with stage I breast cancer (T1a,b,cN0M0; AJCC 2010) diagnosed between January 1991 and December 2009. Further analyses were conducted upon a cohort of 282 patients who were divided between those whose tumors expressed both HR and those with only 1HR. Results: The median age was 54.2 years (29-89). Median follow-up was 9.4±4.4 years (0.2-22.9). Both HR and 1HR were expressed in 242 and 40 patients respectively. Similar adjuvant treatment was administered in both groups although the number of mastectomies was higher in the subgroup with only 1HR (22.5% vs. 5.8%, P =. 0003). Univariate analyses showed no difference between both groups when correlated with age, body mass index, histologic type, T stage, histologic and nuclear grade, mitotic index, vascular invasion, necrosis and margin status. However, 1HR tumors had a higher rate of lymphovascular invasion (21.9% vs. 9.5%, P =.038) and HER2 expression (57.1% vs. 21.9%, P = .035). Treatment failure was more frequent in patients with only 1HR (12.5% vs. 5%, P =.064). Distant progression was also more common in this subgroup (80% vs. 58.3%, P =.334). There were no statistically significant differences in RFS and OS among groups. Conclusions: The expression of only 1HR constitutes a phenotype that could have a more aggressive biology and be associated with higher risk of recurrence than tumors with both receptors. Analysis of more patients, larger tumor size and N1 disease is warranted to confirm this hypothesis and have a better prognostic assessment.
Variations at HER2 and hormone receptor status in primary and metastatic sites of breast cancer patients.
Authors: Alhan Nurcan , Rahatli Samed , Kucukoztas Nadire , Yalcin Selim , Yagmurdur Mahmut Can , Dizdar Omer , Atilgan Alev , Ozdemir Handan , Altundag Ozden , Ozyilkan Ozgur
Published: March 2020

e11023

Background: Evaluation of hormone receptors (ER/PR) and Her2-Neu is important for hormonal and anti-Her2 treatments. The parameters are generally estimated in primary tumors and it is unclear whether re-evaluation of metastatic lesions will be effective during follow-up. Methods: The primary aim of this study was the compare Her2 and HR (ER/PR) status in primary and metastatic tissues of breast cancer patients. HR and Her2 expression in biopsy specimens obtained from primary tumor and their metastatic lesions of 44 breast cancer patients, followed-up during 1995-2010 at Baskent University Hospital were analyzed. Results: Of 44 patients 29.5% were found Her2 (+), 54,5 % ER (+) and 45.4% PR (+) in primary site. Metastatic regions excised or biopsied as following: Bone 31.8% (14/44), liver 27.3% (12/44), skin 25% (11/44), lung 9.1% (4/44), brain 4.5% (2%44), bone marrow 4.5 (2/44), ovaries 4.5% (2/44), stomach, abdominal LAP and pelvic mass 2.3% (3/44). Positification rate of ER status in metastatic sites was detected as 4.5% (2/44), when positive in primary tumors, negatification rate was detected as 20.5%. The positification rate of PR status in metastatic sites, while being negative in primary tissue was 13.6% (6/44); and negativication rate in metastatic lesions, being positive in primary tumor was 27.3% (12/44). The positivication rate of Her2 expression in metastatic lesions while being negative in primary tissue was 4.5% (2/44); and negativication rate while being positive in primary tumor was detected as 13.6% (6/44). When the hormone receptor status and Her2 expression of the patients followed-up are evaluated, receptor variation was detected in 23 of 44 patients. Conclusions: Our study confirms that biological properties of breast cancer may vary among primary tumors and asynchronised metastatic lesions. Further prospective studies are needed to better define the discordance of Her2 or HR status at primary tissue and metastatic sites.
Outcome of breast cancer patients with stage I diesease: A retrospective analysis.
Authors: Ergun Aydin , Kucukoztas Nadire , Yalcin Selim , Rahatli Samed , Babacan Taner , Yagmurdur Mahmut Can , Ozyilkan Ozgur , Dizdar Omer , Altundag Ozden , Altundag Mustafa Kadri
Published: March 2020

e11026

Background: Breast cancer is being diagnosed at earlier stages with the increasing use of screening mammography and public awareness. Treatment of stage I breast cancer is not established strictly and various prognostic and predictive factors are considered in treatment decisions. In this study, we aimed to determine feasible and reliable prognostic factors for using adjuvant chemotherapy in the treatment of stage I breast cancer. Methods: Patients with stage I breast cancer diagnosed in two centers, i.e. Baskent University and Hacettepe University, were retrospectively evaluated. Patient and tumor characteristics as well as patient outcomes in terms of DFS and OS were determined. Results: A total of 614 patients were identified. Median age was 50, and 44% were premenopausal. Patient characteristics were summarized in the table. Median follow-up was 38 months (6-369 mos). 38 patients relapsed on follow-up and 5 patients died. Seven of the relapses was locoregional, 29 were distant, including 10 with bone-only metastases, 19 with visceral metastases. Median DFS was 68 mos. Median OS was not reached. Five year DFS was 92% and 10 year DFS was 83%. 5 year OS was 96.8%. In multivariate analysis including age, hormone receptor status, cerbB2, grade, LV invasion, menopausal status and histological subtype, only grade 3 disease was shown to be associated with significantly increased relapse rate (OR 10, 95% CI; 1.15-86.9) Conclusions: In accordance with the pertinent literature, our findings suggest that tumor grade is strongly associated with higher risk of relapse. Further studies with molecular markers may provide beter prognostication and tailoring treatment according to the risk. [Table: see text]
FDG PET-CT in breast cancer: A single institution experience from India.
Authors: Rao Nalini K , Ajaikumar Basavalinga S , Kallur Kumar G , Sridhar P S , Somorat Bhattacharjee , Radheshyam Nayak , Govindarajan Mallarajapatna , Mahesh Bandemegal , Nagaraj Kanakapura Ramanna
Published: March 2020

e11027

Background: Whole body FDG PET CT is a useful tool in diagnosis, staging and prognosis; and its timely use is critical for early intervention and achieving long term survival in patients with early and advanced breast cancer. Methods: In this observational retrospective study, we report FDG PET CT findings of all breast cancer patients enrolled in our hospital based cancer registry between the years 2008 to 2011. Results: One thousand and fifty three women underwent a total of 1638 scans. Two hundred and forty five scans (14.96%) were done for staging /restaging/diagnosis, 1208 (73.75%) were for response evaluation to chemotherapy and 185 (11.29%) were for surveillance. The median age at diagnosis was 53 years. We identified a possible synchronous breast primary in 28 (2.66%) women and a probable new or existing second non-breast primary in 21(1.99%) women. Internal nodal metastasis was identified in 76 (7.21%) women at diagnosis. There were 26 (2.47%) patients with multicentric tumors. There was an increased uptake in the thyroid gland in 49(2.99%) and in the adrenal in 41 (2.50%) women. There were other random ‘Incidental findings of concern’ in 7 (0.37%) of women, diagnosed either on the CT or PET-CT component. Findings on PET-CT, including- upstaging of the breast primary and unexpected new findings, unrelated to the breast primary, changed the treatment plan in approximately 7% -10% of the patients. We did find that PET-CT did not impact early tumors; however, it did contribute in, 1) the assessment of internal mammary nodes, 2) prognostication based on tumor burden and, 3) aggressive management of oligometastases. Conclusions: Whole body FDG PET CT is a useful tool for staging and prognostication in breast cancer patients. However, the timing of such scans for surveillance needs to be defined for early detection of progression to have an impact on survival.
Clinical and pathological comparison of patients with breast cancer under age 35 with those over age 70.
Authors: Dal Pinar , Rahatli Samed , Kucukoztas Nadire , Yalcin Selim , Dizdar Omer , Altundag Ozden , Ozyilkan Ozgur
Published: March 2020

e11045

Background: Despite intensive treatment given to young breast cancer women, prognosis is stil poor in this group of population. However, older patients seem to have better prognosis. Methods: We performed the retrospective study for 50 women ≤35 yo compared with 50 women ≥70 yo, diagnosed and treated from 1991-2009 at Baskent University Hospitals. Results: Older women were more likely to have lower tumor grades and higher HR positivity, ≤35 years old women were more likely to have Her2 positivity, larger tumor size and metastatic lymph node involvement. Median follow up duration was 21.7 (2-91) months for ≤35 group, whereas it was 36.2 (4-195) months for ≥70 years group. Recurrence was observed in 34% of the young age group and 24% of the older age group. Three patients from the young group and 4 patients for ≥70 years age group died during the follow-up Young breast cancer patients have poor prognosis. Even after adjustment of the data, Overall survival and relapse free survival showed worse prognosis. Normal prognostic factors like tumor size, axillary lymph node involvement and grading can therefore be not the explanation for the more agressive disease progression alone. Older women were more likely to have lower tumor grades and higher hormone receptor positivity, ≤35 years old women were more likely to have Her2 positivity, larger tumor size and metastatic lymph node involvement. Median follow up duration was 21.7 (2-91) months for ≤35 age group, whereas it was 36.2 (4-195) months for ≥70 years group. Recurrence was observed in 34% of the young age group and 24% of the older age group. Three patients from the young group and 4 patients for ≥70 years age group died during the follow-up Young breast cancer patients have poor prognosis. Even after adjustment of the data, Overall survival and relapse free survival showed worse prognosis. Normal prognostic factors like tumor size, axillary lymph node involvement and grading can therefore be not the explanation for the more agressive disease progression alone. Conclusions: There are various reasons such as difficulty in diagnosing the patients the patients at earlier stage because of the higher density of breast tissue at younger age may be one of the reason.
Patient-reported outcomes (PRO) in patients with metastatic breast cancer (MBC) from the VIRGO observational cohort study (OCS).
Authors: Kaufman Peter Andrew , Mayer Musa , Dreyer Nancy A. , Yim Yeun Mi , Yu Elaine , Su Zhaohui , Mun Yong , Sloan Jeff A. , Cleeland Charles S.
Published: March 2020

e11051

Background: Limited data exist on patient (pt) experience and work productivity (WP) in MBC. VIRGO is a prospective OCS following >1200 pts with locally advanced or MBC receiving 1st-line hormonal therapy (HT) or chemotherapy (CT) in a real-world setting. We report baseline characteristics of 277 pts from the VIRGO PRO substudy and correlations between health-related quality of life (HRQoL), symptoms, activities of daily living, and WP. Methods: Symptom severity and interference (MD Anderson Symptom Inventory [MDASI]), functional status (Activity Level Scale [ALS] from the Rotterdam Symptom Checklist) and WP (Work Productivity and Activity Impairment Questionnaire) were assessed. Pts rated their HRQoL during the past week on a scale of 0–10. Results: See table. The five most severe symptoms at baseline were fatigue, decreased sexual interest, disturbed sleep, drowsiness, and emotional distress; these were reported with less severity in the HT cohort (24%-37% vs 42%-59%). Overall MDASI severity and interference correlated with WP measures in the CT (R = 0.46 to 0.78) and HT cohorts (0.36 to 0.94). Mean of the five most severe symptoms also significantly correlated with WP indices (R = 0.47 to 0.66). HRQoL correlated (p < 0.05) with all WP measures (R = -0.46 to -0.56) in the CT cohort and with % impairment while working (R = -0.65) and % overall work impairment (R = -0.71) in the HT cohort. In univariate regression analysis, MDASI symptom interference score was the best predictor of reduced WP (R2 = 0.52 while working; R2 = 0.48 for nonwork activities). Conclusions: MBC pts receiving CT and HT report significant work impairment. Results indicate moderate correlations between WP indices, HRQoL and symptom burden. [Table: see text]
Effect of inhibition of ErbB2-tyrosine kinase domain with lapatinib on cardiac dysfunction compared to the antibody trastuzumab in mice.
Authors: Tocchetti Carlo G. , Coppola Carmela , Rea Domenica , Castaldo Noemi , Guarino Lorena , Barbieri Antonio , Palma Giuseppe , Gala Marianna , Luciano Antonio , Giudice Aldo , Piscopo Giovanna , Capasso Immacolata , Scala Stefania , Monti Maria Gaia , Cittadini Antonio , Iaffaioli Rosario Vincenz , De Lorenzo Claudia , Arra Claudio , Maurea Nicola
Published: March 2020

e11052

Background: Lapatinib (L) inhibits ErbB2-tyrosine kinase domain and has been reported (in the few existing trials) to be associated with a low risk of cardiac dysfunction (2%), while the prototypical Trastuzumab (T) increases the frequency of asymptomatic ejection fraction decrease by 3-18%, and the risk of heart failure by 2-4%. Here, we characterize our L murine cardiotoxicity model. Methods: Cardiac function was measured with fractional shortening (FS) by M-mode echocardiography, and with radial myocardial strain (%) with speckle tracking (ST) in sedated C57BL6 mice (2-4 mo. old) at day 0, and after 2 and 7 days of daily administration of L (100mg/kg/day orally), and in control mice. For comparison we used our well-established models with T (2.25 mg/kg/day, ip), and Doxorubicin (D, 2.17 mg/kg/day ip) as positive control. On excised hearts, we evaluated TNFα and CD68 by immunohistochemistry. Results: FS was reduced with D at 2 days: 52±0.2%, p<.001 vs 60±0.4% (sham), while L and T decreased FS only at 7 days (56±2 and 49±1.5%, respectively, both p<.05 vs 60±0.5% for sham). Interestingly, FS reduction with L was milder (p=.01) than with T. By immunohistochemistry, all treatments increased cardiac inflammation significantly vs controls. In particular, with T more myocytes were positive for TNFα (6±1%), and there were more CD68 cells/mm2 (72±6) compared to L (2±.2% and 27±4, respectively, both p<.02 vs T). D-treated hearts exhibited the highest values. Importantly, from a diagnostic point of view, with ST-echocardiogaphy, myocardial strain was reduced early at 2 days with L and T, predicting cardiotoxicity: 34±7% for L, 44±7% for T (p=NS), both p<.05 vs sham (66±.6%). Conclusions: Specifically targeting the tyrosine kinase domain of ErbB2 with L is less cardiotoxic than T. Nevertheless, both dysfunctions occur later than D. Myocardial strain identifies systolic dysfunction earlier than conventional echo and can be useful to predict cardiotoxicity in these settings. From a clinical point of view, we plan to evaluate the impact of ST echocardiography in early prediction of anti-ErbB2 toxicity in patients, while dissecting myocardial toxicity mechanisms in our animal models.
Trastuzumab-induced cardiotoxicity in early breast cancer: Evaluation of possible risk and protective factors.
Authors: Farolfi Alberto , Melegari Elisabetta , Aquilina Michele , Scarpi Emanuela , Ibrahim Toni , Maltoni Roberta , Sarti Samanta , Cecconetto Lorenzo , Pietri Elisabetta , Fedeli Anna , Faedi Marina , Nanni Oriana , Amadori Dino , Rocca Andrea
Published: March 2020

e11054

Background: Adjuvant trastuzumab improves survival in early breast cancer (EBC) patients (pts). However, trastuzumab-induced cardiotoxicity (TIC) renders it necessary to identify possible risk and protective factors. Methods: A retrospective study was conducted in which medical charts of pts treated with adjuvant trastuzumab were reviewed. Hypertension, smoking history, dysthyroidism, obesity, hypercholesterolemia, diabetes mellitus and anthracycline cumulative dose were considered as potential risk factors. The relationship between the use of beta-blockers (BB), angiotensin-converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB) (either started before or during adjuvant therapy) and TIC development was also evaluated. TIC was defined as an absolute left ventricular ejection fraction (LVEF) decrease ≥15 points from baseline or an absolute LVEF <50%. The term heart failure (HF) referred to the New York Heart Association classification III or IV. Logistic regression was used to assess relative risks. Results: A total of 179 HER2-positive EBC pts (median 54 years, range 30-84) were evaluated. 154 (86%) were treated with anthracycline-based adjuvant chemotherapy. 78 (44%) did not show any risk factors, whereas 101 (56%) had at least one: hypertension (24%), smoking habit (16%), dysthyroidism (18%), obesity (12%), hypercholesterolemia (9%) and diabetes mellitus (4%). Among the 179 EBC pts, 78 (44%, 95% confidence intervals (CI) 37-51%) experienced TIC during their 12-month trastuzumab treatment and only 4 (2%, 95% CI 0-4%) developed HF. 14 pts stopped trastuzumab due to TIC. None of the risk factors described above was correlated with TIC development. A previous anthracycline cumulative dose > 240 mg/m2 conferred an odds ratio of 3.07 compared with treatmemt with lower doses (95% CI 1.29-7.27, p=0.0011). BB, ACEI and/or ARB neither reduced nor increased the risk of TIC. Conclusions: TIC is a frequent, albeit generally mild, adverse event in clinical practice. Closer collaboration between cardiologists and oncologists is needed to better define risk and protective factors of cardiotoxicity in order to avoid trastuzumab-therapy discontinuation.
Mechanisms of resistance to trastuzumab as neoadjuvant therapy in women with HER2-overexpressing operable breast cancer.
Authors: Jinno Hiromitsu , Sato Tomomi , Hayashida Tetsu , Takahashi Maiko , Hirose Shigemichi , Kitagawa Yuko
Published: March 2020

e11060

Background: Despite clinical usefulness of trastuzumab, intrinsic or acquired resistance is a common clinical phenomenon. Potential mechanisms of resistance include aberrant downstream signaling caused by loss of PTEN and/or PIK3CA mutation, alternative signaling from IGF-1R and masking with MUC4. Methods: Patients with operable breast cancer received 12 cycles of weekly paclitaxel (80 mg/m2 IV) plus weekly trastuzumab (4mg/kg loading dose followed by 2 mg/kg IV) before surgery. All tumors were HER2-positive by immunohistochemistry (IHC) or fluorescence in situ hybridization. Expressions of ER, PgR, Ki67, PTEN, phosphorylated IGF-1R (pIGF-1R) and MUC4 were performed by IHC in core needle biopsy samples at baseline. ER and PgR status was assessed using Allred score. For Ki67 labeling index, a total of 400 cells were counted from three consecutive high-power magnifications. PTEN, pIGF-1R and MUC4 expression level was scored semiquantitatively based on staining intensity. PIK3CA mutation status was evaluated by sequencing of PIK3CA exons 9 and 20 using PCR amplification and direct sequencing. Results: Thirty-seven patients were enrolled and assessable for clinical and pathologic responses. The pCR rate was 48.6% (18/37). ER and PgR were positive in 18 (48.6%) and 16 (43.2%) patients, respectively. Negative, moderate and strong membranous expression of MUC4 was observed in 3 (8.1%), 18 (48.6%) and 12 (32.4%) patients, respectively. Membranous staining for pIGF1-R was negative in 24 (64.9%) patients. PTEN loss was observed in 33.3% (8/24) of the tumor examined. PIK3CA sequence analysis of the 13 tumors identified 2 mutations in exon 20 and 2 mutations in exon 9, corresponding to a PIK3CA mutation frequency of 30.8%. MUC4 and pIGF1-R status did not affect the pCR rate. PTEN loss and/or PIK3CA mutation were not significantly associated with pCR rate. pCR rate was significantly correlated with PgR negativity (p=0.004) and higher Ki67 (p=0.01). Conclusions: These data indicate that aberrant downstream signaling caused by loss of PTEN and/or PIK3CA mutation, alternative signaling from IGF-1R and masking with MUC4 were not important mechanisms of resistance to trastuzumab.
Treatment patterns and outcomes with HER2-directed therapy for the treatment of HER2-positive metastatic breast cancer.
Authors: Luthra Rakesh , Fisher Maxine , Brammer Melissa , Lalla Deepa
Published: March 2020

e11063

Background: The goal of this study was to compare treatment patterns and outcomes in patients receiving a HER2 directed therapy for the treatment of HER2+ metastatic breast cancer (mBC). Methods: Female mBC patients (with ≥2 claims with ICD9 diagnosis codes for mBC), age ≥18 years receiving treatment with trastuzumab (T) or lapatinib (L) between 1/1/06 and 8/31/11 were identified in the HealthCore Integrated Research Database (HIRDSM). The earliest mBC claim was defined as index date. Patients with <12 months preindex and ≥6 months postindex continuous eligibility were excluded. Two cohorts were identified: T group received T only; TL group received both L and T (sequentially or together). Treatment duration, metastasis site (mets) at mBC diagnosis, no. of chemotherapy agents, no. of hospitalizations, and total cost of care were assessed in the two groups. Results: Of 1449 patients who received a HER2 directed agent, 1165 were in the T group (mean age 56 yrs) and 284 in the TL group (mean age 54 yrs). T group mets included bone (n=553, 48%), liver (n=336, 29%) and brain (n=283, 24%) mets; TL group had bone mets (n=225, 79%), brain mets (n=167, 59%) and liver mets (n=153, 54%). Mean no. of chemotherapy agents received was lower in T group 3.3 (SD 1.7) compared to TL group 5.8 (SD 2.1) (p=0.0002). The time from 1st mBC diagnosis to treatment with T or L was 117 (SD 217) days in T group and 107 (SD 208) days in TL group. For TL group, time between index date and treatment was 114 (SD 214) days for T and 690 (SD 400) days for L. The mean treatment duration was shorter in T group 417 (SD 366) days compared to TL group 724 (SD 433) days (p<0.0001). TL patients received 579 (SD 402) days of T and 205 (SD 234) days with L. Number of hospitalizations and total cost of care (mean monthly) were 0.1 (SD 0.2) and $12561 (SD $10,975), respectively for T group and 0.1 (SD 0.1) and $13,532 (SD $7,220), respectively for TL group. Conclusions: Mean treatment duration and mean number of chemotherapy agents suggest that the TL group may have received more lines of treatment than the T group. There was no difference in mean monthly costs between the two groups. Medical chart data will be used to confirm treatment patterns and evaluate treatment outcomes in both groups.
Retrospective study of predictors and consequences of nonadherence with lapatinib (LAP) in women with metastatic breast cancer (MBC) who were previously treated with trastuzumab.
Authors: Kartashov Alex , Delea Thomas E. , Sharma Puza P.
Published: March 2020

e11067

Background: LAP, an oral small molecule dual tyrosine kinase inhibitor has been shown to improve time to progression in combination with capecitabine vs. capecitabine alone in women with HER2+ MBC previously treated with trastuzumab, an anthracycline, and taxanes. Data on adherence, persistence, predictors and consequences of non-adherence with LAP in typical clinical practice are scarce. Methods: This was retrospective observational study of predictors and consequences of non-adherence with LAP in women with MBC who were previously treated with trastuzumab using Thomson MedStat MarketScan® Commercial and Medicare claims databases covering 80 million lives. Measures of LAP adherence were calculated from information on pharmacy claims and included medication possession ratio (MPR) and time to first treatment interruption (gap during treatment of 30 days without supply). Predictors of non-adherence to LAP and the association between non-adherence and healthcare utilization and costs were examined using multiple regression analyses. Results: A total of 666 patients met all inclusion criteria. Median follow-up was 12 mos. Mean(SD) MPR was 87% (19%); 22% of patients had MPR<80%. Twenty seven percent of patients had >=1 treatment interruptions during follow-up. Concomitant therapy with a taxane was a predictor of non-adherence (Odds ratio MPR<80%=10.3, 95%CI 3.3 to 31.9, p<0.001). In generalized linear regression models, non-adherence with LAP (1-MPR[range: 0 to 1]) was associated with more physicians' office / hospital outpatient visits (Rate ratio = 1.26, 95%CI: 1.03-1.54, p=0.028). There was a statistically non-significant trend towards an association between adherence and total costs excluding the costs of LAP (Cost ratio = 1.23, 95%CI: 0.93-1.63, p=0.146). Conclusions: Most patients receiving LAP are adherent to therapy, although there is a small group with high non-adherence that may negatively impact healthcare resource utilization. Further research is needed to identify additional predictors of LAP non-adherence so that clinicians may develop strategies to enhance adherence and improve patient outcomes.
The impact of site of care (office clinic versus hospital outpatient) on treatment patterns in HER2-positive breast cancer.
Authors: Parthan Anju , Lalla Deepa , Small Art , Brammer Melissa
Published: March 2020

e11077

Background: This study examines treatment (tx) patterns in patients (pts) with breast cancer (BC) receiving trastuzumab (T) in a physician clinic (MD) & outpatient hospital (HOSP) setting. Methods: Pts ≥18 yrs with BC (≥2 claims with ICD-9-CM 174.xx, ≥30 days apart) and ≥2 T claims from 1/1/2006 to 12/31/2010 were identified from a large US commercial insurance claims database. Pts continuously enrolled for ≥ 6mths before & after index date (date of 1st T claim) were included. Pts receiving T at both sites of care, receiving T before the index date &/or pts with > 1 primary cancer were excluded. Metastatic (mBC) vs. early stage (ESBC) tx was identified by presence of ≥2 claims of metastases after index date. Pts were followed from index date to 30 days after the last infusion prior to a gap of ≥ 90 days, death, disenrollment, or end of study period. Pts were stratified by site of care- MD or HOSP. Descriptive & multivariate analyses were conducted to examine differences in tx patterns (duration and doses/mo) & number of missed doses during the tx period. Results: 2,823 BC pts receiving T were identified; 480 (17%) were treated for mBC. Most patients received T in the MD setting (94% ESBC pts and 87% of MBC pts). Compared to the MD setting, pts treated in the HOSP were more likely to be older (ESBC: 61 vs 53 yrs; MBC: 64 vs 54 yrs; each p <0.001) & have Medicare benefits (ESBC: 54% vs 7%; MBC: 63% vs 9%; each p <0.001). There was no difference in mean baseline Charlson comorbidity index in any group. Mean T duration in HOSP was significantly shorter vs MD among ESBC pts (303 & 333 days, p<0.05) but not MBC pts (313 for HOSP vs 355 days for MD, p>0.05). Compared to the MD setting, HOSP treated patients had more treatment gaps of 30-59 days (ESBC: 58% vs 25%; MBC 56% vs 27%; each p<0.001) and fewer infusions/month (ESBC: mean 1.45 vs 1.99; MBC 1.54 vs 2.07; each p<0.001). In multivariate analyses, infusion counts remained lower among HOSP treated patients (ESBC: IRR 0.74, CI 0.67-0.79; MBC: IRR 0.76, CI 0.66-0.87). Conclusions: MBC and ESBC pts treated in the MD setting were younger and received more infusions with fewer treatment gaps than HOSP pts. Further research assessing the impact of these differences in tx patterns on clinical outcomes is needed.
Cross-sectional observational study to describe the clinicopathological and biological characteristics and the management of patients with HER2+ metastatic breast cancer who experienced complete or partial remission or disease stabilization during at least 3 years: LongHer study.
Authors: Zamora Pilar , Fresno-Vara Juan Angel , Gámez-Pozo Angelo , Perez-Carrion Ramon , Manso Luis , Crespo Massieu Carmen , Mendiola Cesar , Alvarez Isabel , Margeli Vila Mireia , Bayo Calero Juan Lucas , Gonzalez Xavier , Santaballa Ana , Ciruelos Gil Eva Maria , Afonso Gomez Ruth , Lao Romera Juan , Catalan Gustavo , Alvarez Gallego Jose Valero , Miramon Lopez Jose , Salvador Bofill Francisco Javier , Ruiz Borrego Manuel
Published: March 2020

e11081

Background: Trastuzumab has shown an improvement in survival outcomes among patients with HER2+ metastatic breast cancer (MBC). Identification of factors and tumor molecular profiles that may predict long-term remission has become a key-issue. Methods: Multicenter, observational, cross-sectional study. Data were collected from women with HER2+ MBC treated with a trastuzumab-based regimen that experienced CR, PR or SD during at least 3 years. FFPE samples(at least 70% tumor cells)for Microarray Analysis were obtained. L2 Boosting for classification with classical Akaike Information criterion based on the binomial log-likelihood for stopping the boosting iterations algorithm was applied to RNA expression data, to identify variables related to clinical information. Predictive models of long term response were built using a Binary Logistic Regression with the Fisher's scoring. Results: 103 patients.Median age: 58(51-68) years. Metastatic disease diagnosed after a median of 24.7(1.8-51.9) months since primary diagnosis. Predominant type: ductal carcinoma(91.9%) and 59% histological grade III. Hormonal status: Progesterone receptor positive 39.2% and estrogen receptor positive 41.2%. Most common metastatic sites: multiple locations(31.4%), lung(23.5%), bone(14.7%) and liver(13.7%). Overexpression of HER2 assessed by IHC in 98.1% of patients, 91.1% were HER2+(3+) and 18.4% had FISH+ HER2 status. Tumor was positive for p53 (>30%) and Ki67(>20%) in 47.3% and 73.6%. Surgery: 87.4% of patients, 77.5% radical mastectomy. Surgery of metastases was performed on 16.8%. Trastuzumab used in combination in 88.3% with a median number of cycles of 35.5(7.0-46). 68.9% of patients achieved a CR, 20.4% PR and 10.7% had SD, during an overall median time of 55 (43-79) months. 4 patients discontinued trastuzumab due to toxicity. Conclusions: Trastuzumab may provide a substantial long-term survival benefit with a manageable safety profile in these patients. Molecular analysis will be presented in the forthcoming Congress.
The impact on case findings by transferring clinical breast examination skills to female community health volunteers in limited resources country like Nepal.
Authors: Hyoju Sanjiv Kumar
Published: March 2020

e11094

Background: In limited resources countries, patients with breast cancer present to the hospital in the late stage because of lack of awareness, screening program. Clinical Breast Examination (CBE) may be the only means of detecting the breast cancer early in countries with limited resources since mammography is less likely to be cost effective approach and CBE by surgeons are also not possible because of limited health care facility. Hence CBE by FCHVs seems to be more feasible. This study was conducted to observe the skill transfer to FCHVs for detection of clinical abnormalities in breast by determining kappa agreement, sensitivity, specificity, positive predictive value and negative predictive value of CBE by FCHVs considering CBE by the Surgeon as gold standard. Methods: It is a cross-sectional study conducted in Eastern Nepal for period of one year from June 2008 to May 2009. Total 1238 women were examined by both a FCHV and the Surgeon. The results were analyzed to find out interobserver kappa agreement, sensitivity, specificity, positive predictive value and negative predictive value for detection of clinical abnormalities in breast following CBE by FCHVs considering CBE by the Surgeon as gold standard. Results: Total 1238 women received CBE by both a FCHV and the Surgeon. The interobserver kappa agreement for the detection of clinical abnormalities in breast was 67% indicating a good agreement exists between the FCHVs and the Surgeon’s CBE Sensitivity, specificity, positive predictive value and negative predictive values of “FCHVs’ CBE” to detect clinical abnormalities in breast in comparison to “the Surgeon’s CBE” as gold standard were 70%, 95%, 74% and 94% respectively. Conclusions: In view of good CBE skills transfer to FCHVs for detection of clinical abnormalities in breast, the effective training of FCHVs may diagnose and refer the women with clinical breast abnormalities to the hospital for further investigation and treatment.
Smoking and increased breast cancer risk in younger women in Appalachian Kentucky.
Authors: Reddy Indraneel , Shankar Anjali , Mallikarjun Priya , Jabbour Nicola , Dignan Mark
Published: March 2020

e11097

Background: Smoking rates in Kentucky are among the highest in the US. Data from the Centers for Disease Control and Prevention for 2011 showed that in Kentucky 25.2% of the adult population are current smokers compared to 18.4% nationwide. In addition, smoking rates in the Appalachian region are substantially higher than the state rate. Breast cancer rates are also elevated in Appalachian Kentucky, with data from the Kentucky State Cancer Registry for 2004-2008 showing an incidence rate of 67.3 per 100,000 in Appalachia compared to 65.6 per 100,000 for the state. Our objective was to evaluate the association of smoking and breast cancer among women in Appalachian Kentucky. Methods: We reviewed all the breast cancer data from a large community hospital serving the Appalachian areas of Kentucky. Data were collected from the hospital tumor registry for the period 1996-2005 and included demographic characteristics and smoking status, in addition to information about the breast cancer. No personal identifiers were collected. Breast cancers were coded as invasive or non-invasive and smoking status was coded as current smoker, non-smoker or unknown. Results: Data from records of 392 patients were included in the analyses. Over 90% of the breast cancers in the 392 were invasive. Age at diagnosis ranged from 24 to 92 and the mean was 59.9 years (standard deviation= 13.5. 21.2% of the records indicated a family history of breast cancer. Of the 392 patients, 162 (41.3%) were smokers. Analysis of the data by age at diagnosis showed that of the 120 women diagnosed with breast cancer at age less than 65, 46.5% were smokers, compared to 31.3% of those age 65 or older (p=.005, Fisher’s Exact Test). Conclusions: The risk of breast cancer in women under age 65 appears to be associated with smoking in this population. Additional research is needed to more fully explore this association.
Nonpegylated liposomal doxorubicin (nPLD) in neoadjuvant treatment of local advanced breast cancer (LABC) patients (pts).
Authors: Rossi Luigi , Tomao Federica , Papa Anselmo , Zoratto Federica , Ricci Fabio , Spinelli Gian Paolo , Lo Russo Giuseppe , Basso Enrico , Caprio Giuliana , Barberi Simona , Verrico Monica , Giordani Erika , Zaccarelli Eleonora , Rinaldi Giulia , Stati Valeria , Pasciuti Giulia , Strudel Martina , Tomao Silverio
Published: March 2020

e11514

Background: Anthracycline is very effective in treatment of breast cancer, however it can cause cardiac toxicity events. nPLD has greater safety profile and comparable efficacy than conventional anthracyclines. We evaluated safety and efficacy, in neoadjuvant setting, of nPLD in pts with LABC. Methods: 11 pts (median age 57 years). Their clinical stage was: stages IIA and IIB 1 pt respectively, IIIB 7 pts, IIIC 2 pts. 8 pts presented at diagnosis with cT4 disease. All pts were treated with nPLD (50 mg/mq, d1q21) plus Docetaxel (75 mg/mq, d1q21) and Cyclophosphamide (500 mg/mq, d1q21); only 1 pt received Cyclophosphamide, nPLD and Trastuzumab. At beginning of therapy, overall population had left ventricular ejection fraction (LVEF) ≥55%. Results: After a median of 4 chemotherapy cycles, we observed following clinical response: stable disease 2 pts (18%); partial response 7 pts (64%); complete response 2 pts (18%). 9 pts were evaluable for radiological response: objective response rate and clinical benefit were 78 % and 100% respectively. 8 pts underwent surgery, in 3 pts was performed breast-conserving surgery. At the definitive histological examination pathologic stage was: IA 4 pts (50%), IIIA 1 pts (12,5%), IIIB 2 pts (25%) and IIIC 1 pts (12,5%). 2 pts experienced cardiac toxicity: 1 pt had an atrial fibrillation G2 while 1 pt had an symptomatic decline of LVEF G3 after first cycle, causing interruption of treatment. Other pts not showed clinically significant reduction of LVEF (>5%). Conclusions: Despite small number of pts, our experience suggests a safety profile and efficacy of nPLD in neoadjuvant settings for LABC; breast conservation was possible in 3 pts, in other pts (73%) this was not possible mainly for the advanced stage (T4).