Cardiac function in women receiving dual anti-Her2 antibodies (trastuzumab and pertuzumab) combined with chemotherapy for breast cancer.

BACKGROUND: Chemotherapy regimens containing a combination of anti-Her2 antibodies are effective but can be associated with cardiac toxicity. OBJECTIVES: We evaluate the outcome with a particular focus on the cardiac function of patients with Her2 over-expressed breast cancer receiving Chemotherapy regimens combined with Trastuzumab and Pertuzumab in routine clinical practice settings. DESIGN AND METHODS: The initial cohort of patients who started Chemotherapy regimens in combination with Trastuzumab and Pertuzumab before September 2019 in four cancer units were reviewed retrospectively. All patients had regular measurements of left ventricular ejection fraction by Doppler ultrasound. RESULTS: Sixty-seven patients were identified. Chemotherapy regimens in combination with Trastuzumab and Pertuzumab treatment were administered in the neoadjuvant and palliative settings in 28 (41.8%) and 39 (58.2%) patients, respectively. All patients underwent left ventricular ejection fraction assessment prior to starting Chemotherapy regimens in combination with Trastuzumab and Pertuzumab treatment and at 3 and 6 months later. Subsequently, left ventricular ejection fraction was measured at 9, 12, 15, 18, 21, and 24 months as long as patients are still receiving any of the treatment components. Compared to baseline, the mean left ventricular ejection fraction was not significantly different at any of the subsequent time points (range; decrease by 0.936% to increase by 1.087%: T-test P value not statistically significant for all comparisons). Trastuzumab and Pertuzumab administration was withheld temporarily for two patients due to clinically suspected cardiac toxicity which was excluded upon further investigations. In the neoadjuvant cohort, 82.3% of patients were relapse free at 3 years. The median progression-free survival was 20 months, and the median overall survival was 41 months in the palliative cohort. CONCLUSION: In this cohort describing our limited initial experience, dual anti-Her2 antibodies (Trastuzumab and Pertuzumab) combined with chemotherapy is effective and not associated with significant cardiac toxicity when the left ventricular ejection fraction is measured every 3 months. This may suggest that previous concerns about cardiotoxicity may have been overemphasized. Further studies investigating less frequent left ventricular ejection fraction monitoring may be warranted.

Impact of granulocyte-colony stimulating factor on docetaxel-induced febrile neutropenia in patients with breast cancer.

BACKGROUND: Febrile neutropenia (FN) is a life-threatening complication of Docetaxel-based chemotherapy regimens (DBRs). Prophylactic granulocyte-colony stimulating factor (G-CSF) can reduce the risk of FN. This study investigated the effect of G-CSF on FN in patients receiving DBRs for breast cancer. METHODS: Patients treated between 2015 and 2017 were identified from the hospital's pharmacy database and their medical records were examined retrospectively. Data from patients' first four cycles of DBR were collected. FN rate, FN associated length of hospital stay (FN-LOS), and chemotherapy dose modification/delay due to FN were compared between patients who did (G-CSF group) or did not (non-GCSF group) receive prophylactic G-CSF. RESULTS: Of the 276 included patients, 83.3% received a DBR as adjuvant or neoadjuvant therapy, and 50% received docetaxel as combination therapy. Prophylactic G-CSF was administered with the first cycle of a DBR in 69.9% of patients who were significantly less likely to experience FN compared to the non-G-CSF group (6.2% vs. 15.7%; odds ratio: 0.36 [95% CI: 0.16-0.82]; p = 0.020). Collectively and after the 4 DBR treatment cycles, FN rate (4.8 vs. 8.5; odds ratio: 0.54 [95% CI: 0.30-0.97]; p = 0.043) and the mean FN-LOS (3.55 vs. 5.28 days; t = -2.22; p = 0.037) were reduced in the G-CSF group. There was no difference in DBR dose delay/reduction between both groups in cycles 2-4. CONCLUSION: In patients receiving DBRs for breast cancer, prophylactic G-CSF significantly reduced both the rate of FN and duration of hospitalization for FN.

Bone modifying agents for patients with bone metastases from breast cancer managed in routine practice setting: Treatment patterns and outcome.

INTRODUCTION: Bone metastases are common in patients with breast cancer and can lead to pain and skeletal-related events. Bone modifying agents are licensed to be used for these patients. We report the treatment patterns and outcome of zoledronic acid and denosumab in routine practice. METHODOLOGY: Women with bone metastases from breast cancer who have started denosumab or zoledronic acid between 2011 and 2016 were eligible. Those with history of bone modifying agent use prior to diagnosis of bone metastases or with switching treatment between zoledronic acid and denosumab were excluded. Details of patients, tumors, bone modifying agent treatment, selected bone modifying agent toxicity, time to skeletal-related event development, and overall survival were collected retrospectively. RESULTS: In total, 163 women were eligible and included in this analysis. Number of skeletal-related events prior to starting bone modifying agents was 0, 1, 2, and 3 in 91 (55.8%), 53 (32.5%), 13 (8%), and 6 (3.7%), respectively. Zoledronic acid was started for 107 (65.6%) and denosumab for 56 (34.4%) patients. The proportion of patients receiving denosumab increased from 23.1 to 54.3% in years 2011 and 2016, respectively. Dose delay, reduction, and discontinuation due to toxicity were reported more frequently in patients receiving zoledronic acid. Denosumab delayed time to first on-treatment skeletal-related event compared with zoledronic acid (hazard ratio, 0.64; 95% CI, 0.41-0.98; log rank P = 0.044). There was no significant difference in median survival (zoledronic acid: 62 and denosumab: 58 months; log rank P = 0.956). CONCLUSION: Denosumab is superior to zoledronic acid in reducing risk of skeletal-related events and in tolerance profile. However, overall survival is similar with both treatments. Our findings mirror those reported in scrutinized environment of landmark clinical trials.

Etiologic and Clinicopathological Correlates of Gastric Carcinoma in the Egyptian Delta.

We aimed at evaluation of the clinicoepidemiologic data of patients with gastric carcinoma in the Egyptian Delta as regards the etiologic factors, behavior, presenting symptoms, and tumor location, grade, and stage with highlighting of the treatment modalities, survival, and prognostic factors. Three hundred cases with gastric carcinoma were enrolled, diagnosed, and treated in a tertiary oncology center in the Egyptian Delta. Data were collected as regards the etiology, presenting symptoms, family history, comorbid conditions, treatment modalities, responses, recurrences, and survival outcomes. Univariate and multivariate analyses were done to correlate the different clinicopathologic factors with the overall and disease-free survivals. Male to female ratio was 2:1. The median age was 43 years. The main tumor location was in the gastric body. Pain was the commonest presenting symptom (36%). Most of the cases were stage IV (42.0%). Only 49% of cases were operable. On multivariate analysis, age more than 60 years, performance status 3-4, high grade, diffuse type, T4 lesions, N2 and N3, and the presence of metastasis were independently associated with worse OS. We report a clinic-epidemiologic study of gastric carcinoma in the Egyptian delta; the age at presentation was a decade earlier than that recorded in the USA and Europe; most of the cases were sporadic, located mostly at the body. Most of the cases were presented at stage IV with poor response to neoadjuvant therapy with a poorer overall survival than that recorded in the USA and Europe.

Obesity and outcome of post-menopausal women receiving adjuvant letrozole for breast cancer.

INTRODUCTION: Aromatase enzyme activity is predominant in adipose tissue. This has led to speculation that aromatase activity is elevated in obese women and subsequently decreased the clinical activity of adjuvant aromatase inhibitors (AIs) in women with estrogen receptor positive (ER+) breast cancer (BC). We investigated the effect of obesity on the outcome of this population. PATIENTS AND METHODS: Records of 320 consecutive post-menopausal (PM) women with ER+ BC starting single agent adjuvant letrozole between years 2005 and 2014 were retrospectively reviewed. Tumour and patients characteristic including body mass index (BMI) on the day of starting letrozole were extracted. Endpoints of main interest were: (1) Frequency of obesity; (2) relapse-free survival (RFS) in nonobese (G1; BMI < 30) and obese (G2; BMI ≥ 30) patients. RESULTS: Obesity (BMI: 30-34.99) and morbid obesity (BMI ≥ 35) were present in 105/320 (32.8%) and 115/320 (35.9%) women, respectively. Median follow-up of patients was 49 months; RFS at 5 years (G1: 69% versus G2: 78%) and at 8 years (G1: 69% versus G2: 71%). Median RFS is not reached in both groups (Log rank; P = 0.097). There was no correlation between BMI and RFS (correlation coefficient r = 0.075; P = 0.174). CONCLUSION: In this cohort, more than two-thirds of PM women starting adjuvant AIs are obese. Obesity did not adversely affect the outcome of women on adjuvant letrozole.

Serum atrial natriuretic peptide: a suspected biomarker of breast cancer.

AIM OF THE STUDY: To assess serum levels of ANP in breast cancer female patients and its relationship to metastasis and some clinical parameters among those patients. MATERIAL AND METHODS: One hundred breast cancer patients with and without metastasis along with 20 healthy closely matched controls, were enrolled in the present cross sectional study. Background: To assess the serum levels of atrial natriuretic peptide in breast cancer Serum levels of ANP were assessed using ELISA. RESULTS: Mean serum levels of ANP breast cancer patients (13.9 ±10.1 ng/ml) were significantly elevated compared to healthy control group (2.2 ±1.3 ng/ml) (p < 0.001). The metastatic breast cancer patients showed significant elevated ANP levels (17.1 ±8.9 ng/ml) compared to non-metastatic group (6.4 ±8.8 ng/ml) p < 0.001. Within the metastatic group significant difference was detected between de novo metastatic, under follow-up, under hormonal control and locally advanced group (p = 0.007). CONCLUSIONS: This study showed significant elevated levels of ANP in the serum of metastatic breast cancer patients compared to non-metastatic patients. Within the metastatic group the lowest levels were detected in metastatic breast Cancer under hormonal treatment either tamoxifen or aromatase inhibitor.

Assessment of bone health in breast cancer patients starting adjuvant aromatase inhibitors: A quality improvement clinical audit.

INTRODUCTION: Adjuvant Aromatase Inhibitors (AIs) predispose breast cancer patients to accelerated bone loss. Guidelines recommend initial screening and follow up of bone mineral density with dual energy X-ray absorptiometry (DEXA) scan. In this audit we assessed the rate of adherence to these guidelines and introduced awareness measures to improve it. METHODS: All post-menopausal women who started upfront adjuvant AIs (letrozole in all patients) between January 2007 and December 2013 were retrospectively identified. The standard to be audited was "These patients should have a baseline DEXA scan requested within the first 3 months of starting adjuvant AIs therapy". A 90% or more compliance was accepted as satisfactory. Corrective measures in the form of educational and awareness sessions followed by re-auditing of the practice over the subsequent 12 months were planned in case of lower compliance rate. RESULTS: Three hundred and sixty seven eligible patients were identified. Baseline DEXA scan was performed in 188 (51.2%) patients. As planned, this result triggered the conduction of 4 consecutive educational sessions over a period of 2 weeks. Re-auditing the practice in the pre-defined subsequent subjects showed compliance in 47/52 (90.4%) patients. CONCLUSION: This study of a sizable cohort confirms previous observations that adherence to skeletal health guidelines in this patient population is less than adequate. Adherence is improved dramatically by raising the awareness of relevant physicians.

Polymorphisms of glutathione S-transferase π 1 and toll-like receptors 2 and 9: Association with breast cancer susceptibility.

Polymorphisms in antioxidant enzymes and innate immune receptors have been implicated in the development of various types of cancer. The present study aimed to investigate whether polymorphisms of glutathione S-transferase π 1 (GSTP1) and toll-like receptors (TLRs) 2 and 9 are associated with susceptibility to breast cancer among females. The study was conducted on 72 Egyptian female patients with breast cancer, along with 100 healthy volunteers. Polymorphisms of GSTP1 (codon 105 Ile/Val) and TLR9 rs187084 (1237T/C) genes were assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, while the -196 to -174 deletion/insertion (del/ins) polymorphism of TLR2 was detected by PCR. The results indicated a decrease in GSTP1 Val allele frequency in breast cancer patients compared with healthy controls, at rates of 22.9 vs. 32.5%, respectively. In addition, the breast cancer group demonstrated a decreased TLR9 C allele frequency compared with the control group, at rates of 36.1 vs. 51.5%, respectively (P=0.0047). A non-significant difference was detected in the frequency of the TLR2 -196 to -174 del allele in breast cancer patients when compared to normal controls. In conclusion, these results suggested that the GSTP1 Val and TLR9 1237C alleles, but not TLR2 -196 to -174 del, are likely to be associated with breast cancer development among females.

Low-dose versus standard-dose gemcitabine infusion and cisplatin for patients with advanced bladder cancer: a randomized phase II trial-an update.

Prolonged infusion of low-dose gemcitabine and cisplatin (GC) proved to be an effective treatment for patients with advanced bladder cancer. One hundred and twenty untreated patients with stage III/IV bladder cancer were randomized to receive either gemcitabine (250 mg/m(2)) 6-h infusion on days 1 and 8, and cisplatin (70 mg/m(2)) on day 2 every 21-day cycle (arm 1) or gemcitabine (1,250 mg/m(2)) 30-min infusion on days 1 and 8, with the same dose of cisplatin (arm 2). The 92 males and 28 females included in the study had a median age of 62 years (range 40-85 years). Among the 120 patient, complete response was achieved in 11.7 % (7/60 patients of arm 1) and 5 % (3/60 patients of arm 2). Eighteen patients in arm 1 (30 %) and 17 patients (28.3 %) in arm 2 had partial response on therapy. Thus, the overall response rate of patients in arm 1 and arm 2 was 41.7 % (25/60 patients) and 33.3 % (20/60 patients), respectively (p = 0.37). No significant difference in median time to disease progression (26 vs. 24 months, p = 0.4), median survival (12 vs. 16 months, p = 0.8), and 1-year survival (49.9 vs. 54.7 %, p = 0.8) was detected between arms 1 and 2, respectively. Main toxicities were similar in both arms with no statistically significant differences. Low-dose, prolonged infusion gemcitabine in combination with cisplatin is not inferior to the standard GC regimen with favorable toxicity profile and less financial costs.

Hormone receptors and age distribution in breast cancer patients at a university hospital in northern egypt.

INTRODUCTION: Breast cancer is the most common cancer among Egyptian women. The disease is often advanced at diagnosis. Since molecular profiling is not feasible in routine practice, we sought to examine the association of age distribution with hormone receptor profile, disease stage and outcome among Egyptian women. PATIENTS AND METHODS: We conducted a retrospective review of breast cancer patients treated at Mansoura University Cancer Center in the Nile Delta from 2006 through 2011. Age groups were examined in relation to hormone receptors status and tumor clinicopathological criteria. Additionally, the effect of receptor status on disease relapse and disease-free survival was examined with logistic regression and Kaplan-Meier analysis. RESULTS: A total of 263 patients were included in the current analysis. About 66.9% (n = 176) of patients were hormone receptor positive, 14.1% (n = 37) were Her2/neu positive, and 19.0% (n = 50) were triple negative. Median age of the patients was 52 years and was equal across all receptor status types. Triple negative status correlated with increased risk of disease relapse (odds ratio = 1.8, P = 0.03) and with shortened disease-free survival (hazards ratio = 2.6, P < 0.01). CONCLUSION: The age distribution and receptor status pattern in the Nile Delta region does not explain the aggressive behavior of the disease. The age of the patients at diagnosis is older than patients in earlier studies from Egypt emphasizing the importance of implementing mammographic screening programs.