[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).

[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.

[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 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.

[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.

[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.

[Management of bone metastases]. / A csontáttétek kezelése.

The skeleton is the most common site to be affected by advanced breast, prostatic, lung, kidney, thyroid and other solid tumors (in addition to myeloma multiplex). Bone metastases cause significant morbidity with nearly always fatal outcome. Over 600 000 new patients diagnosed in the developed countries yearly. On average every 4-6 months patients suffer from series of severe skeletal complications such as pathologic fractures, spinal cord compression, hypercalcemic events, etc., besides the permanent pain. Local external beam radiotherapy, systemic radioisotope-, endocrine-, and chemotherapy, oral and i.v. bisphosphonates and recently s.c. denosumab are the mainstays of treatment, in addition to pain-killers and other usual "classical" interventions. The modern treatments singificantly reduce the probability of skeletal complications and improve the patients' quality of life and, sometimes, they extend the survival as well. The authors briefly summarize the available treatment options.

[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.

[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.

[Aromatase inhibitors and arthralgia]. / Aromatázgátlók és artralgia.

In several large adjuvant clinical trials it has been demonstrated that substitution (eventually addition) of aromatase inhibitors (AIs) provides an improved outcome of endocrine-sensitive breast cancer over tamoxifen alone. Nevertheless, arthralgia induced by the AIs is one of the most frequent side effects in hormonal therapy. It is characterized by tenosynovial changes and is more frequent in patients in clinical practice than previously appreciated in adjuvant clinical trials. AI-related arthralgia may be related to estrogen deprivation, but estrogen replacement is not an option for these women. Therefore standard painkillers, NSAIDs (COX2 inhibitors), week opioids and other interventions (vitamin D, calcium, bisphosphonates, exercise, acupuncture, complementary and alternative approaches, eventually switch to another endocrine drug) are used for managing this treatment-related side effect, and improve adherence and quality of life among breast cancer survivors.

[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.

[Non-pegylated doxorubicin (Myocet®) as the less cardiotoxic alternative of free doxorubicin]. / A nem pegilált liposzomális doxorubicin (Myocet®), mint a szabad doxorubicin kevésbé kardiotoxikus alternatívája.

Anthracyclines have probably been considered to be the most active agents for the treatment of breast cancer and some other solid tumors and hematological malignancies. However, they are associated with dose-related cardiotoxicity, which can lead to progressive myocardial damage and limits the maximal cumulative dose that can be given. This review focuses on the non-pegylated liposome-encapsulated doxorubicin (Myocet®), which has been developed to increase the therapeutic index of free doxorubicin. The encapsulation of doxorubicin within a macromolecular vector, such as a liposome ("nanoparticle based drug delivery system") reduces its distribution volume, diminishing its toxicity for healthy tissues while increasing the concentration within the neoplastic tissue. The most common adverse event is neutropenia, which is consistent with previous experience with free doxorubicin. Available evidence suggests that the incidence of hematological toxicity is lower than with conventional doxorubicin. Myocet® both as a single agent and in combination is effective and safe with an associated reduction in incidence and severity of cardiac events. Nagykálnai T. Non-pegylated doxorubicin (Myocet®) as the less cardiotoxic alternative of free doxorubicin.

[Chemotherapy of elderly patients with colorectal cancer]. / Idôskorú kolorektális daganatos betegek gyógyszeres kezelése.

Elderly patients will be the largest group of oncology patients in the future. Because of minimal participation of older patients in randomized clinical trials there is a lack of evidence-based data to make correct decisions with regard to chemotherapy and/or targeted therapy in this age group. Elderly patients have similar benefits from systemic therapies as younger counterparts, but many elders have substantial co-morbidities, which may limit the life expectancy and the effectiveness of systemic therapy. Close collaboration between oncologists and geriatrists will help make decisions on the management of elderly patients suffering from cancer.

[The development of the first line treatment of metastatic colorectal cancer (mCRC)]. / A távoli áttétes kolorektális rák (mCRC) elso választású kezelésének fejlodése.

Chemotherapy options of metastatic colorectal cancer (mCRC) have been progressed rapidly in the last years. Besides of the standard fluorouracil/folinic acid treatment some new active agents (oxaliplatin and irinotecan) have been introduced, and more recently the "targeted" biologicals (bevacizumab, cetuximab, panitumumab) have demonstrated their high effectiveness. This review summarizes the development of the first line treatment of mCRC.

Early diagnosis of chemotherapy-induced cardiomyopathy: a prospective tissue Doppler imaging study.

The aim of our study was to compare the applicability of the conventional echocardiography and a novel method, tissue Doppler imaging (TDI) in detection of late or subclinical cardiotoxicity following anthracycline chemotherapy in long-term follow up. Forty women (31 to 65 years) were enrolled, who had not received anthracyclines previously and had normal cardiac function. The control group consisted of 20 healthy persons of similar age range. In addition to standard echocardiographic measurements, each patient underwent specific measurements (E-septum separation, pulmonary venous flow) as well. Furthermore, the myocardial velocity of numerous segments of the mitral anulus obtained with pulsed wave TDI was also detected over a two-year-long period. Systolic left ventricular function did not change significantly either in the study or in the control group. After one year, diastolic left ventricular function was impaired in 39 patients (97.5%), and 29 (72.5%) of these showed clear changes by means of the traditional E/A ratio and TDI. However, in ten patients (25%) the diastolic dysfunction could only be detected with TDI. At the end of the study diastolic dysfunction was detected in each patient, but in 13 patients (32.5%) the relaxation disorder could be revealed only with TDI. Detectable myocardial damage occurred in the study group as a result of anthracycline therapy. Our results confirmed our assumptions that TDI is a more precise and useful examination method than the traditional ones (E/A ratio or deceleration time) to demonstrate isolated diastolic dysfunction. TDI may become a regularly and more widely used noninvasive method to detect subclinical cardiotoxicity emerging after chemotherapy.

[Adjuvant endocrine therapy in postmenopausal hormone-sensitive breast cancer: to start, to switch or to extend?]. / A posztmenopauzális hormonérzékeny emlôrák adjuváns endokrin kezelése: kezdeni, váltani, kiterjeszteni?

From the big randomized clinical trials there are evidences that adjuvant endocrine therapy for hormone-sensitive early breast cancer in postmenopausal women should include an aromatase inhibitor (AI). Anastrozole or letrozole should be used upfront for 5 years (ATAC and BIG 1-98), the sequential approach of tamoxifen for 2-3 years, followed by anastrozole or exemestane for 2-3 years is a reasonable alternative (ABCSG8, ARNO 95, IES, ITA), and mostly in patients with node-positive disease completing 5 years of tamoxifen should be offered letrozole up to 4-5 years (MA-17). In each of these trials incorporation of an AI resulted in significant improvement in study endpoints. Further results will be needed to establish the optimal beneficial effect, use, duration and safety of adjuvant AI therapies.

[The role of ibandronate in the daily oncological practice]. / Az ibandronát helye a napi onkológiai gyakorlatban.

Intravenous ibandronate at a dose of 6 mg every 3-4 weeks in patients with breast cancer and bone metastases produced a significant, 40% reduction in the relative risk of skeletal-related events. Oral ibandronate at a dose of 50 mg once daily for 96 weeks similarly reduced the overall skeletal morbidity, equating to a reduction in the relative risk of skeletal-related events of 38% relative to placebo. Ibandronate was generally well tolerated in clinical trials and their long-term extensions. Both type of administration significantly improve patients' health-related quality of life. There was no evidence of renal toxicity with iv. or oral ibandronate.

[Cardiotoxicity induced by chemotherapy: possibilities of diagnosis]. / Kemoterápia okozta szívizom-károsodás: a diagnosztika lehetoségei.

The authors give a brief summary about the process and significance of cardiotoxicity produced by chemotherapy and irradiation used for malignancy. After the introduction, those invasive and noninvasive processes are put into focus and explained in detail, which are applied in the research of the effects of cardiotoxic chemotherapy. The clinical importance of this research is the life prolongation effect of the treatment, which allows the late-appearing toxic cardiomyopathy, resulting in congestive heart failure and increasing mortality. Summarizing the last decade's progress in research, it is evident that even in the planning of chemotherapy, the cardiovascular risks have to be taken into account, because they can greatly influence the cardiac side effect of the treatment.

[Evolution of adjuvant chemotherapy of breast cancer from Bonadonna to the taxanes]. / Az emlôrák adjuváns kezelésének fejlôdése Bonadonnától a taxánokig.

The author summarizes the progress of adjuvant chemotherapy of breast cancer from the classical Bonadonna-type CMF over the anthracyclines to the taxanes. The CMF regimen represented the prototype of combination chemotherapy which significantly improved early and long term results. After 20 years the patients given adjuvant combination chemotherapy with CMF had significantly better rates of relapse-free survival (p<0.001) and overall survival (p=0.03) compared with no chemotherapy. 6 cycles of CMF was the gold standard of adjuvant chemotherapy in breast cancer for decades. The Milan research group decided in the early 1980s to challange this popular CMF combination by introducing doxorubicin within the adjuvant program. Compared with standard CMF, anthracyclin-containing regimens reduced the annual risk of recurrence by 12% and the annual risk of death by 11%, equating to a 3.2% absolute reduction in recurrence and a 2.7% absolute reduction in mortality at 5 years. This small but real difference seen with regimens containing three or more agents (e.g. CEF and CAF, FAC, FEC, etc.), whereas 4 cycles of 2-drug regimens (e.g. AC or EC) appears to be equivalent to 6 cycles of CMF. Among the novel chemotherapeutic drugs introduced in the 1990s the taxanes have emerged as the most powerful compounds in breast cancer. Several large, adjuvant clinical trials are currently ongoing or have recently completed accrual. The available results from innumerable clinical studies are still inconclusive and do not support the routine use of taxanes in the adjuvant setting - with the exception of the BCIRG 001 docetaxel trial, in which significant improvement was documented in disease free survival with 6 x TAC compared with 6 x FAC (82% vs 74%). Studies on the effect of the new trastuzumab (an antibody against the extracellular domain of the HER2) in adjuvant setting was initiated in early 2000. The Herceptin adjuvant trial programme is extensive, involving more than 12,000 patients worldwide. This trials will potentially offer many women with HER2-positive disease the chance of improved survival.

[Selective estrogen receptor modulators (SERMs) in the practice]. / Szelektív ösztrogénreceptor-modulátorok (SERM-ek) a gyakorlatban.

Selective estrogen receptor modulators (SERMs) represent a growing class of compounds that act as either estrogen receptor gonists or ntagonists in tissue-selective manner. SERMs with the appropriate selectivity profile offer the opportunity to dissociate the favorable bone and cardio-vascular effects of estrogen from its unfavorable stimulatory effects on the breast and uterus. The triphenylethylene drug tamoxifen proved to be invaluable to treat and protect against breast cancer and bone loss, probably reduces cardiovascular risk, but had side effects on uterus similar to natural estrogens. The tamoxifen derivate toremifene is also used to treat breast cancer, but has less effect on bone. The non-steroidal benzothiophene derivate, raloxifene, is the best SERM available thus far. It has the potential to prevent breast cancer (like tamoxifen), but has better profile in its actions on bone and cardiovascular system (produces a rapid reduction of serum cholesterol, decreases fibrinogen and lipoprotein, improves the vascular epithelial function, attenuates vascular intimal thickening, etc.). It does not increase the incidence of endometrial cancer. Compounds of this class are the first step in developing the perfect hormone replacement and other multitargeted therapy. This review summarizes the recent important knowledge about SERMs.