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.

Response to Induction Neoadjuvant Hormonal Therapy Using Upfront 21-Gene Breast Recurrence Score Assay-Results From the SAFIA Phase III Trial.

PURPOSE: Luminal, human epidermal growth factor receptor 2-negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT). MATERIALS AND METHODS: The SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2-negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo. The objectives of this interim analysis were to assess the feasibility of upfront RS determination on core biopsies in the Middle-East and North Africa region and evaluate the efficacy of induction NAHT in patients with an RS < 31. RESULTS: At the time of this interim analysis, 258 patients with relative risk were accrued, including 202 patients (RS < 31% to 78.3%) treated with induction NAHT and 182 patients evaluable so far for response. The feasibility of performing the Oncotype DX assays on core biopsy specimens was optimal in 96.4% of cases. Overall, 93.4% of patients showed hormone sensitivity and no difference in NAHT efficacy was noticed between RS 0-10, 11-25, and 26-30. Interestingly, patients with high RS (26-30) showed a trend toward a higher major response rate (P = .05). CONCLUSION: The upfront 21-gene assay performed on biopsies is feasible in our population and has allowed us to select patients with high hormone sensitivity (RS < 31). This approach could be an alternative to upfront surgery without significant risk of progression, particularly during pandemic times.

Neuroendocrine tumor of the kidney: Diagnostic challenge and successful therapy.

The management of gastrointestinal and pancreatic (GEP) neuroendocrine tumors (NETs) has evolved over the recent decade. Primary renal NETs are extremely rare as neuroendocrine cells are not recognized in the normal renal parenchyma. We report a case of primary renal NET characterized by the initial diagnostic challenges. Recurrent and metastatic disease was managed along the lines of management of GEP-NETs, leading to prolonged progression-free survival.