Radiotherapy of Breast Cancer-Professional Guideline 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

The international radiotherapy (RT) expert panel has revised and updated the RT guidelines that were accepted in 2020 at the 4th Hungarian Breast Cancer Consensus Conference, based on new scientific evidence. Radiotherapy after breast-conserving surgery (BCS) is indicated in ductal carcinoma in situ (stage 0), as RT decreases the risk of local recurrence (LR) by 50-60%. In early stage (stage I-II) invasive breast cancer RT remains a standard treatment following BCS. However, in elderly (≥70 years) patients with stage I, hormone receptor-positive tumour, hormonal therapy without RT can be considered. Hypofractionated whole breast irradiation (WBI) and for selected cases accelerated partial breast irradiation are validated treatment alternatives to conventional WBI administered for 5 weeks. Following mastectomy, RT significantly decreases the risk of LR and improves overall survival of patients who have 1 to 3 or ≥4 positive axillary lymph nodes. In selected cases of patients with 1 to 2 positive sentinel lymph nodes axillary dissection can be substituted with axillary RT. After neoadjuvant systemic treatment (NST) followed by BCS, WBI is mandatory, while after NST followed by mastectomy, locoregional RT should be given in cases of initial stage III-IV and ypN1 axillary status.

Hazai tapasztalatok metasztatikus kolorektális karcinóma bevacizumabbal kiegészített indukciós kemoterápiás kezelésével (AVACONT vizsgálat).

The primary aim of AVACONT was to collect data in the course of routine oncological care from patients with metastatic colorectal cancer (mCRC) treated with bevacizumab supplemented fluoropyrimidine-based chemotherapy doublet in an open, multicentre, observational study in Hungary. Primary endpoint of the study was to determine progression-free survival (PFS). The Full Analysis Set (FAS) comprised 280 patients. Median PFS calculated from enrolment was 270 days in the FAS population. The metastatic involvement of the liver or more than one organ significantly decreased (250 and 245 days), while a clinical response achieved significantly increased (partial response: 404, complete response: 623 days) the mPFS calculated from enrolment. PFS calculated from the start of the first-line treatment was significantly decreased by the presence of mutant RAS gene (481 vs. 395 days). The results confirm the efficacy, known prognostic factors and safety profile of bevacizumab in combination with chemotherapy dosed during standard oncology care in Hungarian centres.

Pathologic Complete Response Rates After Neoadjuvant Pertuzumab and Trastuzumab with Chemotherapy in Early Stage HER2-Positive Breast Cancer - Increasing Rates of Breast Conserving Surgery: A Real-World Experience.

Purpose: The neoadjuvant use of pertuzumab and trastuzumab with chemotherapy improves the pathologic complete response (pCR) in early HER2+ breast cancer. The aim of this study was to determine the pCR rate obtained with dual HER2 blockade in routine clinical practice. The secondary and tertiary objective was to investigate the impact of neoadjuvant systemic therapy (NST) on performing breast-conserving surgery and survival data. Methods: This was a multicentre, retrospective, observational study in patients with stage II and III HER2+ early breast cancer who received pertuzumab and trastuzumab-based NST. Data were collected from patients' medical records. Results: Eighty-two patients were included in the study treated in 8 cancer centers in Hungary between March 2015 and January 2020. The study included women with a median age of 50.3 years. The majority of the patients (95%) received a sequence of anthracycline-based chemotherapy followed by docetaxel. pCR was achieved in 54% of the cases. As a result of NST a significant increase of conservative breast surgeries (33% vs. 3.6% planned, p = 0.0001) was observed. Ki67 expression and neutrophil-to-lymphocyte ratio (NLR) significantly predicted pCR. None of the variables were independent predictors of DFS. Conclusion: The pCR rate achieved in our study demonstrates the reproducibility of trial data in a real-world population. The rate of breast-conserving surgery was significantly increased.

[Secondary lung cancer risk after breast cancer radiation therapy. The benefits substantially overweight the minimal disadvantages]. / Az emlorák sugárkezelése utáni másodlagos tüdorák kockázata. Az elonyök lényegesen meghaladják a minimális rizikót.

Considerable evidence supports the rationale for postoperative radiotherapy after breast cancer surgery. Moreover, local tumour control affects survival too. High-dose irradiation is inherently associated with an increased risk of secondary malignancies in the long run. This radiobiological phenomenon raises the question whether it is worth taking this hazard, and the exact level of the risk of a secondary malignancy should be clarified. Answering these questions is important, regarding the large population size of breast cancer survivors, as well as patients' improving survival rates and time. The postoperative radiation load to the ipsilateral lung tissue can be reduced, but it is still significant. The current literature review aims to evaluate the risk of secondary lung cancer associated with breast cancer- specific radiotherapy. Published evidence suggests that the benefits of postoperative radiotherapy following breast cancer surgery are much higher than the minimal risk of secondary lung cancer associated with this management strategy.

[4th Hungarian Breast Cancer Consensus Conference - Radiotherapy guidelines]. / IV. Emlorák Konszenzus Konferencia ­ Sugárterápiás irányelvek.

The radiotherapy (RT) expert panel revised and updated the RT guidelines accepted in 2016 at the 3rd Hungarian Breast Cancer Consensus Conference based on new scientific evidence. Radiotherapy after breast-conserving surgery (BCS) is indicated in ductal carcinoma in situ (St. 0), as RT decreases the risk of local recurrence (LR) by 50-60%. In early stage (St. I-II) invasive breast cancer RT remains a standard treatment following BCS. However, in elderly (≥70 years) patients with stage I, hormone receptor positive tumour hormonal therapy without RT can be considered. Hypofractionated whole breast irradiation (WBI) and for selected cases accelerated partial breast irradiation are validated treatment alternatives of conventional WBI. Following mastectomy RT significantly decreases the risk of LR and improves overall survival of patients having 1 to 3 or ≥4 positive axillary lymph nodes. In selected cases of patients with 1 to 2 positive sentinel lymph nodes axillary dissection can be substituted with axillary RT. After neoadjuvant chemotherapy (NAC) followed by BCS WBI is mandatory, while after NAC followed by mastectomy locoregional RT should be given in cases of initial stage III-IV and ypN1 axillary status.

[Oral contraception and the risk of breast cancer. Review of the literature]. / Orális fogamzásgátlás és emlõrákkockázat. Irodalmi áttekintés.

At present an estimated hundred millions of women worldwide use oral contraception, but the influence of hormonal contraception on carcinogenesis of breast is not fully understood. Previous studies of breast cancer risk show inconsistent findings - from zero elevation to approximately 30%-40% increase in risk. The beneficial effect on ovarian and endometrial cancer risk is apparent. In this literature review we attempt to determine effects of oral contraception in relation to the risk of breast cancer. The risk increased with longer duration of use, but absolute increase is very small. "Beneficial effects of OCs on the gynecological cancers thus outweighed adverse effects." (Vessey).

Everolimus Plus Exemestane vs Everolimus or Capecitabine Monotherapy for Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer: The BOLERO-6 Randomized Clinical Trial.

Importance: Everolimus plus exemestane and capecitabine are approved second-line therapies for advanced breast cancer. Objective: A postapproval commitment to health authorities to estimate the clinical benefit of everolimus plus exemestane vs everolimus or capecitabine monotherapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Design: Open-label, randomized, phase 2 trial of treatment effects in postmenopausal women with advanced breast cancer that had progressed during treatment with nonsteroidal aromatase inhibitors. Interventions: Patients were randomized to 3 treatment regimens: (1) everolimus (10 mg/d) plus exemestane (25 mg/d); (2) everolimus alone (10 mg/d); and (3) capecitabine alone (1250 mg/m2 twice daily). Main Outcomes and Measures: Estimated hazard ratios (HRs) of progression-free survival (PFS) for everolimus plus exemestane vs everolimus alone (primary objective) or capecitabine alone (key secondary objective). Safety was a secondary objective. No formal statistical comparisons were planned. Results: A total of 309 postmenopausal women were enrolled, median age, 61 years (range, 32-88 years). Of these, 104 received everolimus plus exemestane; 103, everolimus alone; and 102, capecitabine alone. Median follow-up from randomization to the analysis cutoff (June 1, 2017) was 37.6 months. Estimated HR of PFS was 0.74 (90% CI, 0.57-0.97) for the primary objective of everolimus plus exemestane vs everolimus alone and 1.26 (90% CI, 0.96-1.66) for everolimus plus exemestane vs capecitabine alone. Between treatment arms, potential informative censoring was noted, and a stratified multivariate Cox regression model was used to account for imbalances in baseline characteristics; a consistent HR was observed for everolimus plus exemestane vs everolimus (0.73; 90% CI, 0.56-0.97), but the HR was closer to 1 for everolimus plus exemestane vs capecitabine (1.15; 90% CI, 0.86-1.52). Grade 3 to 4 adverse events were more frequent with capecitabine (74%; n = 75) vs everolimus plus exemestane (70%; n = 73) or everolimus alone (59%; n = 61). Serious adverse events were more frequent with everolimus plus exemestane (36%; n = 37) vs everolimus alone (29%; n = 30) or capecitabine (29%; n = 30). Conclusions and Relevance: These findings suggest that everolimus plus exemestane combination therapy offers a PFS benefit vs everolimus alone, and they support continued use of this therapy in this setting. A numerical PFS difference with capecitabine vs everolimus plus exemestane should be interpreted cautiously owing to imbalances among baseline characteristics and potential informative censoring. Trial Registration: ClinicalTrials.gov identifier: NCT01783444.

[Alcohol and breast cancer. A short survey]. / Alkohol és emlõrák. Rövid áttekintés.

Regular consumption of alcohol increases the risk of developing (one or more of) several malignant conditions: the frequency of tumours in the aerodigestive tract, in the liver, in the colorectal region and in the breast is increased. The principal carcinogen component of alcoholic drinks is ethanol itself; the effect is unmistakably proportional to the daily/weekly dosage. Under the influence of alcohol-dehydrogenase, ethanol will metabolise to acetaldehyde, which is a known carcinogen. Among other things chronic alcohol consumption promotes the production of endogen hormones, affects the insulin-like growth factor-1, alters several biological pathways, raises oxidative stress, and damages the genes. Even modest daily alcohol intake will increase the risk of breast cancer.

An open-label, dose-ranging study of Rolontis, a novel long-acting myeloid growth factor, in breast cancer.

This randomized, open-label, active-controlled study investigated the safety and efficacy of three doses of Rolontis (eflapegrastim), a novel, long-acting myeloid growth factor, versus pegfilgrastim in breast cancer patients being treated with docetaxel and cyclophosphamide (TC). The primary efficacy endpoint was duration of severe neutropenia (DSN) during the first cycle of treatment. Patients who were candidates for adjuvant/neoadjuvant TC chemotherapy were eligible for participation. TC was administered on Day 1, followed by 45, 135, or 270 µg/kg Rolontis or 6 mg pegfilgrastim on Day 2. Complete blood counts were monitored daily when the absolute neutrophil count (ANC) fell to <1.5 × 109 /L. Up to four cycles of TC were investigated. The difference in DSN (time from ANC <0.5 × 109 /L to ANC recovery ≥2.0 × 109 /L) between the Rolontis and pegfilgrastim groups was -0.28 days (confidence interval [CI]: -0.56, -0.06) at 270 µg/kg, 0.14 days (CI: -0.28, 0.64) at 135 µg/kg, and 0.72 days (CI: 0.19, 1.27) at 45 µg/kg. Noninferiority to pegfilgrastim was demonstrated at 135 µg/kg (P = 0.002) and 270 µg/kg (P < .001), with superiority demonstrated at 270 µg/kg (0.03 days; P = 0.023). The most common treatment-related adverse events (AEs) were bone pain, myalgia, arthralgia, back pain, and elevated white blood cell counts, with similar incidences across groups. All doses of Rolontis were well tolerated, and no new or significant treatment-related toxicities were observed. In Cycle 1, Rolontis demonstrated noninferiority at the 135 µg/kg dose and statistical superiority in DSN at the 270 µg/kg dose when compared to pegfilgrastim.

[The post-treatment cognitive impairment ("chemobrain") in breast cancer patients. Short review.] / Az emlõrák kemoterápiáját követõ kognitív mûködési zavar, a "chemobrain". Rövid áttekintés.

With the continually growing number of cancer survivors in the past decades there is an increased interest in understanding and treating the adverse events of cancer therapy, which damage the survivor's quality of life. Post-treatment cognitive impairment (chemobrain) is well known in women with breast cancer and other patients with malignancy. The goal of the current short review is to arouse the caregivers' attention to the not severe, but real problem.

[Treatment of bone metastases: bisphosphonates and denosumab]. / Daganatos csontáttétek gyógyszeres kezelése: biszfoszfonátok és denosumab.

Some disseminated tumor cells (as "seeds") feel well in the skeletal tissue, as a "soil", but the humoral crosstalk between tumor cells and bone cells disrupts the normal bone homeostasis (remodeling), which leads to a vicious circle, the multiple bone metastatic disease. The tumor cells could stimulate bone resorption, bone neo-formation or both, characteristic of the primary tumor. This usually incurable condition involves serious consequences, as fractures, pain, surgeries, irradiations, plegias, hypercalcemia, etc. (skeletal-related events, SREs), which destroy the quality of life. Targeting bone resorption with bisphosphonates or RANK ligand dependent mechanism could improve the rate of serious SREs and disease-free survival.

The MAGIC survey in hormone receptor positive (HR+), HER2-negative (HER2-) breast cancer: When might multigene assays be of value?

BACKGROUND: A modest proportion of patients with early stage hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer benefit from adjuvant chemotherapy. Traditionally, treatment recommendations are based on clinical/pathologic criteria that are not predictive of chemotherapy benefit. Multigene assays provide prognostic and predictive information that can help to make more informed treatment decisions. The MAGIC survey evaluated international differences in treatment recommendations, how traditional parameters are used for making treatment choices, and for which patients treating physicians feel most uncertain about their decisions. METHODS: The MAGIC survey captured respondents' demographics, practice patterns, relevance of traditional parameters for treatment decisions, and use of or interest in using multigene assays. Using this information, a predictive model was created to simulate treatment recommendations for 672 patient profiles. RESULTS: The survey was completed by 911 respondents (879 clinicians, 32 pathologists) from 52 countries. Chemo-endocrine therapy was recommended more often than endocrine therapy alone, but there was substantial heterogeneity in treatment recommendations in 52% of the patient profiles; approximately every fourth physician provided a different treatment recommendation. The majority of physicians indicated they wanted to use multigene assays clinically. Lack of reimbursement/availability were the main reasons for non-usage. CONCLUSIONS: The survey reveals substantial heterogeneity in treatment recommendations. Physicians have uncertainty in treatment recommendations in a high proportion of patients with intermediate risk features using traditional parameters. In HR+, HER2- patients with early disease the findings highlight the need for additional markers that are both prognostic and predictive of chemotherapy benefit that may support more-informed treatment decisions.

Capecitabine in Combination with Docetaxel in First Line in HER2-Negative Metastatic Breast Cancer: an Observational Study.

Due to the limited experience with capecitabine plus docetaxel (XT) combination in the first-line treatment of metastatic breast cancer in Hungary, the main objective of the study was to analyze the effectiveness and tolerability of XT therapy. A prospective, open-label, non-randomized, single-arm, multicenter, observational study was designed. All female patients were eligible whose metastatic breast cancer could be treated with the XT protocol according to the summary of product characteristics of the drugs. The median progression free survival was 9.9 ± 3.0 months. Time to treatment failure was 4.6 ± 5.1 months on average. The overall response rate was 28.9 %, the clinical benefit rate was 73.3 %. The treatment was discontinued in 35.6 % of patients due to disease progression and in 20.0 % due to adverse events (AE). 33 patients with a total of 73 AEs have been reported, and 13 of them had serious adverse events (SAE). The efficacy and the safety profile of XT chemotherapy proven in the study are consistent with the results demonstrated in randomized trials. First-line XT chemotherapy effectively improves the PFS in metastatic breast cancer.

[Cachexia in cancer patients]. / A daganatos kahexia.

About 50% of all patients with cancer eventually develop anorexia/cachexia syndrome, which represents a complex clinical syndrome occurring in several illnesses, including cancer. The syndrome is characterized by systemic inflammation and primarily loss of body fat and body mass. In this review we shortly summarize the pathomechanism of anorexia/cachexia syndrome and list the current pharmacological approaches.

[3rd Hungarian Breast Cancer Consensus Conference - Radiotherapy Guidelines]. / III. Emlõrák Konszenzus Konferencia - Sugárterápiás irányelvek.

The radiotherapy expert panel revised and updated the radiotherapy (RT) guidelines accepted in 2009 at the 2nd Hungarian Breast Cancer Consensus Conference based on new scientific evidence. Radiotherapy of the conserved breast is indicated in ductal carcinoma in situ (St. 0), as RT decreases the risk of local recurrence by 60%. In early stage (St. I-II) invasive breast cancer RT remains a standard treatment following breast conserving surgery. However, in elderly (≥70 years) patients with stage I, hormone receptor positive tumour hormonal therapy without RT can be considered. Hypofractionated (15×2.67 Gy) whole breast irradiation and for selected cases accelerated partial breast irradiation are validated treatment alternatives of conventional (25×2 Gy) whole breast irradiation. Following mastectomy RT significantly decreases the risk of locoregional recurrence and improves overall survival of patients having 1 to 3 (pN1a) or ≥4 (pN2a, pN3a) positive axillary lymph nodes. In selected cases of patients with 1 to 2 positive sentinel lymph nodes axillary dissection can be omitted and substituted with axillary RT. After neoadjuvant chemotherapy (NAC) followed by breast conserving surgery whole breast irradiation is mandatory, while after NAC followed by mastectomy locoregional RT should be given in cases of initial stage III-IV and ypN1 axillary status.

[Fulvestrant (Faslodex®) for hormone sensitive breast cancer. A review]. / Fulvestrant (Faslodex®) hormonérzékeny emlorákban. Áttekintés.

Endocrine agents are well established standards of care in hormone-sensitive postmenopausal breast cancer. The pure estrogen receptor antagonist (down-regulator) fulvestrant after binding to the ER induces its conformational change which disrupts ER signal and accelerates ER degradation. Fulvestrant is devoid of partial agonist activity. In unselected patients there was no difference in TTP between "standard dose" fulvestrant and aromatase inhibitors, but in first-line treatment of advanced breast cancer the elevated dose of fulvestrant may delay progression and may extend the overall survival compared with aromatase inhibitors.

[Historical overview and the current practice of intracavitary treatment of cervical and endometrial cancer in the Oncoradiology Center of Budapest]. / A méhtest- és méhnyakrák intrakavitális kezelésének történeti áttekintése és jelen gyakorlata a Fõvárosi Onkoradiológiai Központban.

The aims of our study were to describe the history and development of intracavitary brachytherapy in the treatment of gynecological tumors, to introduce our current practice for intracavitary brachytherapy treatments based on CT planning. Gynecological intracavitary brachytherapy has been applied in our department since the early 1930s. After a long development it has been completely renewed by 2014. In our center definitive and/or preoperative gynecological HDR-AL brachytherapy treatments were given to 25 patients (13 corpus uterine cancer patients and 12 cervical cancer patients) during the period of 01. 01. 2014-31. 01. 2015. In each case, target volumes were planned by CT images, DVH (dose volume histogram) analysis was performed in order to calculate the radiation tolerance dose of rectum and urinary bladder. Evaluation was performed by the EclipseTM 11.0.47. brachytherapy treatment planning system. During the definitive treatments of the 13 uterine cancer patients the D2cc value related to rectum tolerance was 66.3 GyEQD2 (46-91 Gy). The average D2cc value of urinary bladder tolerance was 76.5 GyEQD2 (30-112 Gy). CI was 0.72 (0.6-0.95). Average value of COIN was 0.57 (0.35-0.78). Compared to the prescribed dose D100 and D90 values were given in ratios. Compared to the volume which receives 100% of reference dose V150 and V200 values were also given in ratios. D100 and D90 were calculated to be 0.66 (0.47-0.97) and 0.91 (0.8-1.25). V150 and V200 volumes were 0.11 (0.04-0.18) and 0.06 (0.02-0.1). During the definitive treatments of 12 cervical cancer patients the D2cc value related to rectum tolerance calculated by DVH was 75.2 GyEQD2 (60-82 Gy). The average D2cc value of urinary bladder tolerance was 85 GyEQD2 based on DVH. CI was 0.66 (0.42-0.76). Average value of COIN was 0.52 (0.32-0.78). Mean value of DHI was 0.46 (0.27-0.54). D100 and D90 were calculated to be 0.72 (0.57-0.89) and 0.91 (0.84-1.11). V150 and V200 volumes were 0.057 (0.02-0.13) and 0.02 (0.002-0.06). During treatments no severe side effects were found. During gynecological intracavitary HDR therapies the calculated dose of the target volume can be given safely using the EclipseTM 11.0.47. brachytherapy planning system and CT-based planning. CT-based treatment planning provides optimal safety for organs at risk, acceptable doses for rectum and urinary bladder while the target volume receives the proper prescribed dose.

[Vitamin D and breast cancer]. / D-vitamin és emlorák.

The active form of vitamin D, in conjunction with his own receptor, affect a multitude of biological processes in the cell (inter alia it influences the expression of oncogenes and tumor suppressor genes). There is an increasing volume of scientific publications examining the relationships between serum vitamin D levels, vitamin D supplementation and malignant diseases. Some articles suggest inverse relationship between the low serum levels of vitamin D and the breast cancer risk and mortality, whilst other publications do not support this view. Thus the present opinion is conflicted. Vitamin D can exert a beneficial influence on the symptoms and outcomes of a large number of ailments, but its role in affecting cancer is still not completely clear.

[Postoperative radiotherapy of breast cancer and cardiotoxicity]. / Posztoperatív emlobesugárzás és cardiotoxicitas.

Cardiac complications may present a particular problem following radiation treatment applied to the mediastinum and thoracic wall (and especially to the left breast). Exposure of the heart during radiotherapy increases the risk of ischemic heart disease occurring generally years after the treatment. The incidence of radiation cardiotoxicity depends on various factors related to oncological therapies and the patient (details of radiotherapy, age, gender, comorbidities, smoking habits, etc.). Until recently the majority of clinical studies reported increased cardiac morbidity in patients receiving radiation treatment of the chest wall and the breast. Due to modern methods, however, postoperative chest wall and left breast irradiation is much safer today than previously. In order to avoid cardiotoxicity, adherence to clinical practice guidelines for chemo- and targeted therapy of breast cancer, use of the most advanced irradiation procedures, regular monitoring of patients, and close cooperation between cardiologists and oncologists are all recommended.