Abstract
Trastuzumab has improved the prognosis of HER2 positive breast cancer, but cardiotoxicity remains a concern. We aimed to identify risk factors for trastuzumab-induced cardiotoxicity, with an ...emphasis on the HER2 Ile655Val single nucleotide polymorphism. This single-center case–control study included 1056 patients with early-stage HER2 positive breast cancer that received adjuvant trastuzumab. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) > 15% in patients without previous cardiomyopathy, or > 10% in patients with baseline LVEF of < 50%. Patient characteristics and cardiac parameters were compared in 78 (7.38%) cases and 99 randomly assigned controls, and the polymorphism was genotyped using real-time polymerase chain reaction. Cardiotoxicity was independently associated with advanced age (
P
= 0.024), lower body mass index (
P
= 0.023), left breast involvement (
P
= 0.001), N3 status (
P
= 0.004), diabetes (
P
= 0.016), and a family history of coronary artery disease (
P
= 0.019). Genotype distribution was as follows: A/A (Ile/Ile) was found in 111 (62.7%) patients, A/G (Ile/Val) in 60 (33.9%) patients, and G/G (Val/Val) in 6 (3.4%) patients. The genotype was not associated with cardiotoxicity or the severity of heart failure, reversibility, and recovery time. We found no association between the HER2 Ile655Val polymorphism and trastuzumab-induced cardiotoxicity; therefore, we do not recommend routine cardiotoxicity-risk stratification using this polymorphism.
"Basal-like" (BL) morphology and the expression of cancer testis antigens (CTA) in breast cancer still have unclear prognostic significance. The aim of our research was to explore correlations of the ...morphological characteristics and tumor microenvironment in triple-negative breast carcinomas (TNBCs) with multi-MAGE-A CTA expression and to determine their prognostic significance. Clinical records of breast cancer patients who underwent surgery between January 2017 and December 2018 in four major Croatian clinical centers were analyzed. A total of 97 non-metastatic TNBCs with available tissue samples and treatment information were identified. Cancer tissue sections were additionally stained with programmed death-ligand 1 (PD-L1) Ventana (SP142) and multi-MAGE-A (mAb 57B). BL morphology was detected in 47 (49%) TNBCs and was associated with a higher Ki-67 proliferation index and histologic grade. Expression of multi-MAGE-A was observed in 77 (79%) TNBCs and was significantly associated with BL morphology. Lymphocyte-predominant breast cancer (LPBC) status was detected in 11 cases (11.3%) and significantly correlated with the Ki-67 proliferation index, increased number of intratumoral lymphocytes (itTIL), and PD-L1 expression. No impact of BL morphology, multi-MAGE-A expression, histologic type, or LPBC status on disease-free survival was observed. Our data suggest that tumor morphology could help identify patients with potential benefits from CTA-targeting immunotherapy.
Body composition has been studied relatively recently as part of oncology trials in different types of tumors. There are numerous studies that define the impact of chemotherapy side effects on the ...quality of life (QoL) of breast cancer patients, however, there are few studies that analyze the impact of body composition on the QoL of premenopausal patients in the course of cytotoxic treatment. The study was performed on a sample of premenopausal patients treated with neoadjuvant or adjuvant AC chemotherapy for early-stage breast cancer at Day Hospital of the Department of Medical Oncology, University Hospital for Tumors in Zagreb. The study included 68 patients, median age 46.6 years. Analysis of the QoL questionnaires and their association with body composition indicated several interesting results. At the beginning of treatment, most pronounced was the connection between body composition and physical and sexual functioning and hair loss, while in subsequent treatment cycles the effect on other QoL subdomains, in particular fatigue and diarrhea, was more pronounced. In conclusion, we found body composition to have a significant impact on certain QoL subdomains during treatment.
High infiltration by tumor-infiltrating lymphocytes (TILs) is associated with favorable prognosis in different tumor types, but the clinical significance of their spatial localization within the ...tumor microenvironment is debated. To address this issue, we evaluated the accumulation of intratumoral TILs (itTILs) and stromal TILs (sTILs) in samples from 97 patients with early triple-negative breast cancer (TNBC) in the center (sTIL central) and periphery (sTIL peripheral) of tumor tissues. Moreover, the presence of primary and secondary lymphoid aggregates (LAs) and the expression levels of the cancer testis antigen (CTA), NY-ESO-1, and PD-L1 were explored. High infiltration by itTILs was observed in 12/97 samples (12.3%), unrelated to age, Ki67 expression, tumor size, histologic type and grade, and LA presence. NY-ESO-1 was expressed in tumor cells in 37 samples (38%), with a trend suggesting a correlation with itTIL infiltration (p = 0.0531). PD-L1 expression was detected in immune cells in 47 samples (49%) and was correlated with histologic grade, sTILs, and LA formation. The presence of primary LAs was significantly correlated with better disease-free survival (DFS) (p = 0.027). Moreover, no tumor progression was observed during >40 months of clinical follow up in the 12 patients with high itTILs or in the 14 patients with secondary LAs. Thus, careful evaluation of lymphoid infiltrate intratumoral localization might provide important prognostic information.
Oxaliplatin is part of the standard chemotherapy regimens for treating colorectal carcinoma. Pulmonary fibrosis is a serious but rare side effect of oxaliplatin treatment, which resulted in patient ...death in more than half of the reported cases. The precise pathophysiological mechanism of this phenomenon has not been clarified yet. Analysis of the reported cases strongly suggests that early diagnosis and immediate corticosteroid treatment are crucial for better prognosis. Here we report a case of pulmonary fibrosis related to the FOLFOX regimen in a patient with early colorectal carcinoma.
- Sunitinib is an orally administered multikinase inhibitor. This therapy can provoke uncommon side effects such as pancytopenia, tumor lysis syndrome, cardiac disorders, thromboembolic incidents, ...intestinal perforation, pancreatitis, acute renal failure, etc. We report a case of a 63-year-old female admitted to the hospital due to abdominal pain, nausea, vomiting and elevated blood pressure. One month earlier, sunitinib therapy for metastatic renal cell carcinoma was initiated. During the first cycle of therapy, after three weeks of sunitinib 50 mg daily, symptoms started and she stopped taking the drug. At admission, laboratory tests revealed elevated serum and urine amylase, C-reactive protein, urea and creatinine, and lowered platelet and leukocyte counts and hemoglobin value. Urine test showed proteinuria, erythrocyturia, leukocyturia and granulated cylinder. The patient was diagnosed with acute pancreatitis grade III, acute renal failure grade II, pancytopenia and urinary infection, and was hospitalized for five days. She was treated symptomatically and with antibiotic therapy because of persistently elevated C-reactive protein and pathologic urinary sediment, which led to subjective and clinical improvement. Acute pancreatitis, renal insufficiency and pancytopenia are rarely described side effects of sunitinib therapy, and clear connection between these conditions and drug activity is not yet determined. Medical specialists who prescribe and treat patients with sunitinib should be aware of the possible occurrence of these conditions and perform regular checkups of sunitinib treated patients.
Pazopanib is multitargeted tyrosine kinase inhibitor used for the treatment of metastatic renal cell carcinoma. Hair colour change is a common side effect of pazopanib therapy which usually develops ...gradually during few months of therapy. We report a case of the patient who developed multiple pazopanib side effects followed by rapid overnight hair and eyebrow depigmentation after only few weeks of therapy. In our research, we found no literature data of rapid loss of hair pigment due to therapy with any of listed multitargeted tyrosine kinase inhibitors. To the best of our knowledge, this is the first such case being reported. We presume that summation of different mechanisms probably led to rapid hair depigmentation. Considering the fact that pazopanib treatment was very effective in our patient, this side effect could be a good predictor of therapy success, although it presents very stressful event for patient and his family.
Standard chemotherapy for early breast cancer consists generally of an anthracycline – taxane - based regimen, preferably in sequence. Anthracyclines are among the most active cytotoxic drugs against ...breast cancer. Nevertheless, benefits attained by the use of the more potent anthracycline schedules must be balanced against increased short – and long – term toxicity, and treatment options must be individualized for each patient. Authors review available data regarding anthracycline efficacy and toxicity in the early breast cancer setting and the potential directions for future research.
•
Anthracyclines are one of the most effective drugs against breast cancer.
•
Anthracyclines and taxanes for early breast cancer reduce mortality.
•
Anthracyclines raise some concerns about cardiotoxicity and secondary leukemia.
•
Controversy remains regarding risk/benefit for the use of adjuvant anthracyclines.
Triple-negative breast cancer (TNBC) occurs in around one-sixth of all breast cancer (BC) patients, with the most aggressive behavior and worst prognosis of all BC subtypes. It is a heterogeneous ...disease, with specific molecular characteristics and natural dynamics of early recurrence and fast progression. Due to the lack of biomarkers or any valid treatment targets, it can only be treated with classic cytotoxic chemotherapy. We analyzed a cohort of 152 patients, median age 58 years, diagnosed with and treated for early stage TNBC at the university Hospital for Tumors, Sestre milosrdnice university Hospital Centre, Zagreb, Croatia, during the 2009-2012 period. Patients were treated with primary surgical approach, adjuvant chemotherapy and adjuvant irradiation. We observed a relatively large proportion of locally advanced TNBC at diagnosis, with large tumor size and nodal involvement, with high grade and high proliferation index Ki67. Patient age, tumor size and lymph node involvement, as expected, were significant and clinically most important prognostic factors for 5-year disease-free survival (67%; 95% CI 60%-75%) and overall absolute survival rate (74%; 95% CI 66%-81%). Key words: Triple negative breast cancer; Early disease; Adjuvant treatment; Tumor size; Lymph node; Disease free survival; Overall survival; Prognostic factor
PDF
