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.
Knowledge about the patient's experience and perception of side effects and their impact on daily life is crucial for the adequate planning of interventions to provide the highest attainable levels ...of quality of life during oncology treatment. We conducted a study on consecutive samples of 69 early breast cancer patients treated with four cycles of neoadjuvant or adjuvant anthracycline-based chemotherapy. Patients completed the questionnaire about side effects experienced after the previous cycle of chemotherapy. The questionnaire was a modified PRO for the evaluation of treatment toxicity consisting of 18 questions related to the very common and common side effects of doxorubicin and cyclophosphamide, valued from 0 to 3 according to the subjective assessment of the patient. During the same cycles of therapy, data were also collected by the physician who completed a questionnaire consisting of the same questions as the questionnaire for patients, on the same scale. Most of the side effects reported by patients were mild to moderate in intensity, while physicians reported side effects much less frequently. The results also indicated a disproportionate reporting, in which physicians reported statistically significantly fewer side effects than patients. This study reported a level of disagreement between patients and physicians in the experience of therapy toxicity. In conclusion, use of PRO in clinical practice can help us avoid physician subjectiveness in the estimation of side effects and determine the group of patients who can benefit from additional and individualized supportive care measures, which could lead to better adherence to therapy and ultimately best outcomes.
Body composition changes could indicate health conditions and potential health risks. Although several methods are currently available for quantitative assessment, each has limitations. Indirect ...methods are most frequently used because of their availability and simplicity. One of those methods, which found wide use in clinical trials and everyday clinical practice and was found to be of great value in oncology patients, is bioelectrical impedance (BIA). Assessed muscle volume and mass, measured by BIA, were associated with chemotherapy toxicity and overall prognosis, regardless of the primary tumor site. It has been shown that calculated phase angle could be a strong prognostic factor for a particular endpoint and an independent prognostic factor in patients with advanced malignancies. Body composition was also found to correlate with the quality of life (QoL) of patients with cancer, and several studies have shown a significant impact on various QoL subdomains. Measuring body composition and the information it provides could be used for the development of different clinical interventions that can help cancer patients live longer and better lives.
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.
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
Tumor stimulates specific innate and acquired immune mechanisms. Main carriers of body’s immune response to tumor are T lymphocytes and main mechanism is killing of tumor cells by cytotoxic T ...lymphocytes CD8 +. In some cases, immune system can also have a protumor role, which is a paradox, given that it is known that the inflammatory state promotes tumor growth. One of the major characteristics of tumors is the evading of immune response, in particular by mechanisms of inhibition of active antitumor immune response via two major physiological inhibitory signals, CTLA-4 and PD1 / PDL1. Blockade of these checkpoints, that are T cell inhibitory mechanisms, has recently yielded best results in an immunotherapy approach to cancer treatment. Immune infiltrate in the tumor, as evidence of existence of an active intrinsic response of the organism, is heterogeneous, and composition often differs between different tumors and tumor cells, and mainly divides into two main cell lines: lymphoid and myeloid. On type of cell lines in the immune infiltrate and their activation and orientation depends the clinical response in different tumors. It is well known that immune infiltrate, especially tumorinfiltrating lymphocytes (TILs), can be predictive of response to therapy and have a prognostic role. In some solid tumors they are a good sign, while in some they signal worse prognosis. Numerous studies have evaluated role of lymphocytic infiltrate in breast cancer (BC) and, based on this knowledge, first consensus on standardization of TILs evaluation in solid tumors has been established on the BC model. Prognostic role of TILs in triple-negative breast cancer has received the most attention.
Androgen receptors (AR) are ligand-dependent nuclear transcription factors. These are steroid receptors, similar to estrogen receptors (ER). They are expressed in numerous cells in the body, with ...different constructive roles. AR signalling can be involved in the development of a variety of human malignant tumors, such as prostate cancer, bladder, liver, salivary glands, kidney, lung, melanoma, sarcoma, breast cancer, and many others. The role of AR is most clear and today best explained in prostate cancer. The mechanism of AR signalling in other human epithelial tumors is still quite unclear and the effects are different to entirely opposite in different tumors. In breast cancer, AR are the most commonly expressed receptors, but still with an incompletely clear role, prognostic and predictive significance. The expression of AR in triple-negative breast cancer (TNBC) is highly variable. Despite the marked differences in the results of the various analyzes, they appear to have a beneficial effect on the prognosis and are potentially the target of antihormone therapy for treatment of TNBC in the future.
Abstract
INTRODUCTIONAnalyzes reported to date on TIL in TNBC have evaluated mostly stromal (sTIL) and possibly intratumoral TIL (iTIL), but none evaluated TIL spatially, separately in compartments ...of central tumor (CT) and invasive margin (IM). Also, none evaluated connection between TIL and other clinicopathological factors.
METHODSWe retrospectively analyzed consecutive sample of 152 early TNBC patients treated at our institution 2009-2012. TIL were assessed morphologically, by hematoxylin - eosin (HE), using standard formalin - fixed - paraffin - embedded (FFPE) samples, according to recommendation of International Working Group for Evaluation of TIL, both sTIL and iTIL, spatially, in compartments of CT and IM. Available clinicopathological variables were analyzed, and correlations of all paramethers were calculated.
RESULTSMorphological analysis of TIL spatially by compartments showed as follows: median overall sTIL content was 19%, iTIL 5%, TIL in CT 5%, TIL at IM 18%, sTIL in CT 5%, iTIL in CT 1%, sTIL at IM 30%, and iTIL at IM 5%. Intermediate or high TIL content, defined as ≥10% was present in 48% cases of sTIL in CT, 23% of iTIL in CT, 86% of sTIL at IM, and in 47% of iTIL at IM cases. Quarter of patients had TIL>50% in any of four compartments. There was statistically significant positive correlation between sTIL in CT and age and menopausal status, and also tumor size (T), but w/out correlation to histologic subtype, nodal (N) status, grade, and Ki67; iTIL in CT were statistically significantly positively correlated to histologic subtype (precisely to NOS subtype), but negatively to age and menopausal status, exactly opposite to sTIL in this section, and w/out correlation to other tumor characteristics, such as T, N, grade or Ki67; sTIL on IM, as well as iTIL on IM, showed statistically significant correlation to grade and Ki67, and no correlation to age and menopausal status.
DISCUSSIONSection analysis reveals higher density of TIL content at IM, which directs attention towards this neglected tumoral compartment and it's possible role. It also shows, although in small numbers, that possibly iTIL, especially those at IM, could actually not only, as thought so far, serve as ,,satellites“ to sTIL, but an entirely autonomous, and even opposite biomarker. Moreover, all that could be concluded from just a simple and cheap HE morphological analysis of standard tumor specimen.
Citation Format: Ana Tecic Vuger, Robert Separovic, Ljubica Vazdar, Mirjana Pavlovic, Sanda Sitic, Ingrid Belac-Lovasic, Damir Vrbanec. Clinical validity of compartmental analysis of tumor-infiltrating lymphocytes (TIL) in triple-negative breast cancer (TNBC) - The key is in spatial morphology? abstract. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-56.
Invasive ductal carcinoma is the most common type of breast cancer and accounts for about 70-85% of all invasive breast carcinomas. It primarily metastasizes to the bone, lungs, regional lymph nodes, ...liver and brain. Most of breast cancer recurrence occurs within the first 5 years of diagnosis, particularly for ER negative disease. Gastrointestinal tract involvement is very rare and is detected in only 10% of all the cases, and it usually derives from lobular breast cancer rather than the much more common cell type of ductal breast cancer. Early diagnosis is very important because it enables prompt and adequate choice of treatment and improves patient’s long-term prognosis. In this report we describe an unusual case of obstructive jaundice caused by metastases from invasive ductal breast cancer to the lymph nodes of the hepatoduodenal ligament with extramural compression of the distal common bile duct and tumor invasion to the lumen of the duct. Our goal is to emphasize possible diagnostic pitfalls and increase the clinical awareness and the importance of intensive follow-up in patients with breast cancer, even years after the initial diagnosis.
Abstract only
e12571
Background: Little is known about correlation of tumor infiltrating lymphocytes (TIL) and androgen receptors (AR) and their joint effect on early triple-negative breast cancer ...(TNBC) prognosis. Analyzes to date evaluated mostly stromal TIL (sTIL) and intratumoral (iTIL), but not separately in central tumor (CT) and invasive margin (IM). Methods: We retrospectively analyzed consecutive sample of 152 early TNBC patients treated at our institution 2009-2012. TIL and AR were assessed using standard FFPE samples, TIL according to International Working Group for Evaluation of TIL recommendation, sTIL and iTIL in CT and IM, and AR by immunohistochemistry. Results: Median age was 58, 84% NOS, median T 2.2cm, 41% N+, 22%, 59% and 19% in stage I, II and III, respectively. Radical mastectomy was performed in 39%, adjuvant chemotherapy in 88% and radiotherapy in 74% of patients. Positive AR defined as ≥1% nuclear-stained cells, were expressed in 31%, and AR≥10% in 26% of patients. Median TIL content was: sTIL 19%, iTIL 5%, TIL in CT 5%, at IM 18%, sTIL in CT (CTs) 5%, iTIL in CT (CTi) 1%, sTIL at IM (IMs) 30%, and iTIL at IM (IMi) 5%. Prevalence of intermediate or high TIL content, defined as ≥10% was: CTs in 48%, CTi in 23%, IMs in 86%, and IMi in 47% of cases. In bivariable analysis all TIL indicators were significantly associated with longer OS, while AR was not. After adjustment for potential confounders using Cox proportional hazard regression, significant predictors of OS were sTIL (p0.007), IM TIL (p0.002), IMs (p0.001), and IMi (p0.030). In all cases higher TIL content was associated with longer OS. Although AR was not significant predictor of OS, it's interactions with TIL IMs and IMi was. There was no significant difference in OS between patients with high IMs and low IMs and AR0, but those with high IMs and AR≥1 had HR0.22 (p0.045) for death compared to patients with low IMs and AR0. Also, no difference for high IMi and low IMi and AR0, but patients with high IMi and AR≥1 had HR0.10 (p0.028) for death compared to patients with low IMi and AR0. Conclusions: Section analysis reveals frequent intermediate to high density and statistically significant prognostic impact of TIL on IM. That directs question towards role of different tumor compartments. Furthermore, combination of high expression of IMs and IMi with AR≥1 appears to be associated with longer OS than in patients with high IMs and IMi but with AR0. The correlations between AR and all TIL studied are extremely small, indicating their independence, but if so, their interaction in impact on OS is particularly interesting.
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