Metastatic breast cancer still remains an incurable disease, requiring lifelong treatment. Introduction of targeted therapy into clinical practice has radically changed treatment approaches of HER2-positive breast cancer, making it possible to significantly increase the life expectancy. The treatment algorithm for HER2-positive metastatic breast cancer appears to be quite clear and is reflected in both international and Russian recommendations. To assess actual clinical practice in the Russian Federation, a survey study “Therapy of Her2-positive breast cancer” was conducted. This publication presents results dedicated to the treatment of metastatic HER2-positive breast cancer. 50 specialists from 43 cities took part in the survey. Only heads of departments or their deputies who were personally involved in determining the treatment for patients were allowed to participate. Expertise of this level allows us to reliably assess the actual clinical practice that has developed in the Russian Federation and determine directions for optimizing therapeutic approaches. Despite ongoing questions about the availability of drugs, doctors primarily focus on the effectiveness of treatment. The main first-line therapy in the Russian Federation is the combination of trastuzumab with pertuzumab. However, experts noted that in conditions of unlimited access to drugs, the number of prescriptions for this regimen in the first line would increase by 13%. Doctors also agree that the use of a subcutaneous form of this combination of drugs would optimize the treatment process. Trastuzumab emtansine remains the standard of second-line therapy and, according to the survey results, almost all patients for whom it is indicated receive this type of therapy. Experts predict more frequent use of trastuzumab emtansine in first-line therapy, given the widespread use of neoadjuvant regimens with pertuzumab. The most significant changes are expected in the third line of therapy with the introduction of the new conjugate – trastuzumab deruxtecan. The survey results demonstrate high awareness and commitment of physicians to modern principles of treatment of HER2-positive mBC.

The polar division of breast cancer into HER2-positive and HER2-negative subtypes has long remained clinically significance. However, up to 60% of HER2-negative tumors have HER2 receptor expression assessed by immunohistochemistry as 1+ or 2+. In the absence of gene amplification, such tumors are classified as HER2-low. Сlassical anti-HER2 agents have not improved treatment outcomes for these tumors. The development of a new generation antibody-cytostatic conjugate, trastuzumab deruxtecan, targeting the HER2 receptor, is changing diagnostic approaches and clinical practice in the treatment of metastatic HER2-low breast cancer. The results of the phase III DESTINY-Breast04 study of trastuzumab deruxtecan in patients with metastatic breast cancer with low HER2 expression became a real revolution. The median progression-free survival in the cohort of patients receiving trastuzumab deruxtecan was 9.9 months versus 5.1 months in the group of patients receiving standard chemotherapy at the physician’s choice (RR 0.50; 95% CI 0.40–0.63, P = 0.003). An objective response during therapy with trastuzumab deruxtecan was recorded in 52.3% of cases versus 16.3% in the standard treatment group. Therapy with the new drug demonstrated a favorable safety profile and did not reduce the quality of life. In this publication, we present our own experience of treating a patient with metastatic luminal HER2-low breast cancer with trastuzumab deruxtecan. Despite the aggressive course, the number of previous lines of therapy and massive liver damage, the use of trastuzumab deruxtecan made it possible to control the disease for 2 years while maintaining a high quality of life for the patient. Trastuzumab deruxtecan is a new effective treatment option for HER2-low metastatic breast cancer.

Adjuvant therapy with trastuzumab made a significant contribution to improving disease-free and overall survival rates in patients with HER2-positive breast cancer. However, in a number of clinical situations the risk of disease recurrence remains increased. Carrying out neoadjuvant treatment followed by post-neoadjuvant therapy, depending on the degree of pathomorphological response, is the modern standard, allowing to cure a significantly larger number of patients. This became possible thanks to the expansion of the arsenal of terget anti-Her drugs and the introduction into real clinical practice of double anti-HER2 blockade (trastuzumab + pertuzumab) and an antibody conjugate with a cytostatic drug – trastuzumab emtansine. To assess actual clinical practice in the Russian Federation, a survey study “Therapy of HER2-positive breast cancer” was conducted. The survey involved 50 specialists from different regions of the country who are directly involved in developing a treatment plan for patients, which allows them to reflect the preferences of leading chemotherapists regarding tactics for HER2-positive breast cancer. This publication reflects the results of part of the survey, devoted to the choice of adjuvant and post-neoadjuvant therapy for HER2-positive breast cancer. Identified a clear positive trend in favor of neoadjuvant treatment followed by post-neoadjuvant therapy using modern targeted drugs such as pertuzumab and trastuzumab emtansine. The survey results show that 68% of patients with RCB-II–III residual tumor receive post-neoadjuvant trastuzumab emtanzine, in 2021 this figure was only 24%. The absolute majority of patients who have not received neoadjuvant therapy, but have N2–3 stage, receive double anti-HER2 therapy with trastuzumab + pertuzumab in the adjuvant setting. High adherence to the therapy was noted, as 97% of patients complete the planned course of T-DM1, and 91.2% of patients complete a year of adjuvant anti-HER2 therapy. These figures are noticeably higher than the indicators of registration studies. Issues of effectiveness come to the fore in choosing therapy. Issues of drug availability remain relevant, but are not decisive. The survey also revealed factors that were not obvious at first glance and influenced treatment results.

The median overall survival for patients with metastatic triple-negative breast cancer is about 12-14 months. Chemotherapy has been the only treatment option for this tumour subtype for a long time, irrespective of immunological and genetic characteristics. Straightforward therapy algorithms have not been defined, and the optimum sequencing of chemotherapy regimens is left to the discretion of the attending physician. Today, impressive findings from clinical studies on the use of immunotherapy and targeted therapy for cancer using PARP inhibitors reflect in current guidelines, raising the chances of patients to prolong life and maintain its high quality. Thus, the use of immunotherapy as first-line treatment of PD-L1-positive tumours allowed to significantly increase the overall survival of patients for the first time in many years. And the use of PARP inhibitors in carriers of BRCA1/2 germline mutations not only significantly prolongs progression-free survival, but also improves quality of life versus standard chemotherapy regimens. The benefit is also observed in patients with an aggressive course of the disease such as damage to the visceral organs and the central nervous system. The presence of BRCA1/2 germline mutations in the genes, damage to the CNS and visceral organs is associated with an extremely unfavourable prognosis and a significant decline in life expectancy. However, a high-quality diagnosis before initiation of treatment, creating proper treatment plans and the use of modern opportunities can improve the outcomes of treatment. The article discusses possible treatment options for metastatic TNBC, reflects current guidelines on the use of immuno- and targeted therapy. A clinical case report of the treatment of a patient with a significantly aggravated history and an aggressive course of TNBC is presented. The patient with visceral metastases, brain damage and early progression after primary treatment has been receiving therapy for two years, while maintaining a satisfactory quality of life.

Trastuzumab deruxtecan is a new generation Her2-directed antibody-cytostatic conjugate. The unique structure of the molecule, innovative pharmacokinetic and pharmacodynamic properties of the drug allows its effect to be extended not only to the target cells, but also to nearby tumour cells, causing their death. This phenomenon has become known as the abscopal effect, due to which the drug demonstrates effectiveness regardless of the degree of Her2 expression. In clinical trials, trastuzumab deruxtecan therapy significantly outperformed the standard treatment options in patients with Her2-positive breast cancer. Thus, the median time to progression was 17.8 months in patients who were exposed to multiple lines of therapy, including trastuzumab-emtansine, vs 6.9 months in the control group treated with the combination of capecitabine and anti-Her2 agents (RR 0.36, 95% CI 0.28–0.45), which has resulted in a significant prolongation of patients’ lives. The median overall survival reached 39.2 months, while it remained at the level of 26.5 months in the control group (RR 0.6575; 95% CI 0.5023–0.8605; p = 0.0021). In a direct comparison of treatment, trastuzumab deruxtecan was superior to trastuzumab emtansine, significantly increasing the median progression-free survival by 4 times: 28.8 vs. 6.8 months (RR 0.33, 95% CI 0.26–0.43). It also had advantages in terms of objective response rates, quality of life measures, and overall survival. Trastuzumab deruxtecan demonstrated high efficacy in the treatment of HER2-low tumours (Her2-low mBC), surpassing the standard chemotherapy options in all evaluated parameters in pre-treated patients. This article presents the results ofthe main clinical trials of trastuzumab derukstecan, additionally discusses its efficacy in CNS metastatic lesions, highlights the safety issues of the drug.

The development and introduction into widespread practice of anti-HER2 agents has changed the natural course of HER2-positive breast cancer, significantly increasing the chance of cure in early forms and significantly increasing the life expectancy of patients with metastatic disease. The results of clinical trials indicate a significant increase in the frequency of achieving complete pathological regress and improved survival rates when using the combination of trastuzumab + pertuzumab in neoadjuvant therapy for HER2-positive breast cancer, which is reflected in modern national and international guidelines. However, the use of drugs in real clinical practice is associated with a whole range of factors and may differ from standard recommendations. To understand the situation in the Russian Federation, a survey study ‘Therapy of HER2-positive breast cancer’ was conducted. 50 specialists – heads of drug therapy departments and/or their deputies who are directly involved in the development of a treatment plan for patients, were involved in the survey. It allows to reflect the preferences of leading chemotherapists regarding treatment strategies for patients with HER2-positive breast cancer in Russian Federation. This publication highlights the results of a survey on the prescription of neoadjuvant therapy for primary resectable and locally advanced unresectable HER2-positive breast cancer. Most experts prefer to use combinations with pertuzumab. In real clinical practice, 62% of patients receive dual anti-HER2 therapy. In the future, experts are ready to increase the percentage of prescribing pertuzumab for early HER2-positive breast cancer for more 16–20%. Based on the results of large randomized trials, this should improve long-term outcomes in one of the most aggressive forms of breast cancer.

PARP inhibitors have been successfully used in the treatment of BRCA-associated metastatic breast cancer in recent years. Adjuvant therapy for gBRCAm carriers with HER 2-negative high-risk early-stage breast cancer has become a new indication for the use of olaparib. This publication highlights the results of an updated analysis of the OlympiA trial that has changed clinical practice. Adjuvant treatment with olaparib for 1 year signifiantly increased survival rates. Four-year IDFS for the olaparib group was 82.7 % vs 75.4 % for placebo group. Four-year OS was 89.8 % in the olaparib group and 86.4 % in the placebo group. The treatment has a favorable safety profie and does not reduce quality of life. Despite impressive results the OlympiA study raises many questions about the possibilities of integrating PARP inhibitors into modern standards for the treatment of early breast cancer. The main points of contention and possible ways to resolve them are discussed in this review.

The life expectancy of patients with metastatic luminal HER 2-negative breast cancer has stagnated at the level of 40 months for many years. The introduction of CDK4/6 inhibitors into practice has changed the standards of therapy, providing not only a significant increase in the time without progression while maintaining a high quality of life, but also significantly increasing overall survival. The presence of liver metastases determines an extremely unfavorable prognosis, with GH+HER 2-mBC reducing life expectancy to a median of 21 months. Endocrine therapy combined with ribociclib significantly increased overall survival rates on average per year, reaching medians of 36.1 and 46.5 months, depending on the line of treatment. This publication is devoted to liver metastases in breast cancer, in particular in the luminal HER 2-negative subtype. Epidemiological aspects are considered, the possibilities of modern systemic therapy are evaluated. A clinical case of successful therapy with ribociclib in a young patient with liver damage is presented.

Before the development and implementation of the first PI3K inhibitor (alpelisib), the presence of a mutation in the PIK3CA gene had only prognostic value: it determined the unfavorable course of luminal HER2-negative metastatic breast cancer (testing for mutations was not part of routine screening methods). Achievements in the treatment of HR+HER2- mBC are primarily associated with the use of CDK4/6 inhibitors, which allowed not only a significant increase in the median progression-free survival while maintaining high quality of life, but also significantly increased overall survival of patients with luminal HER2-negative metastatic breast cancer. However, subgroup analyses demonstrate that the presence of the PIK3CA mutation is an independent factor in decreasing progression-free time and overall survival, even in patients treated with CDK4/6 inhibitors. Mutations of the PIK3CA gene are diagnosed in 30-40% of luminal metastatic breast cancer patients, they are associated with an increased risk of relapse and disease progression, are associated with a significant reduction in survival rates and treatment effectiveness, and determine the development of primary and secondary resistance to endocrine therapy. Standard endocrine therapy with fulvestrant combined with alpelisib has significantly improved treatment outcomes in patients with HR+HER2-metastatic breast cancer with the PIK3CA mutation who previously received treatment for advanced disease or had progression during adjuvant therapy. This combination is now included in all major international guidelines and is a priority therapy option. Testing for PIK3CA mutations is the current diagnostic standard in luminal HER2-negative mBC. The review presents an update of the main clinical trials with alpelisib, treatment results from real clinical practice, and also considers aspects of use in pretreated patients with different medical history. The article outlines the main recommendations for the prevention and correction of adverse events, and presents our own experience of using alpelisib in a patient with a classic course of breast cancer with a PIK3CA mutation.

Introduction . PARP inhibitors demonstrated high efficacy in BRCA1/2-associated Her2-negative metastatic breast cancer (BC). They were included in the current standard chemotherapy regimen and recognized as a priority option for the treatment of such tumours following the results of clinical studies. Aim . Review the experience with talazoparib (Talzenna) in the real-world clinical practice of 6 medical centers in Russia. Materials and methods . The review included data from 29 patients with HER2-negative metastatic breast cancer associated with a gBRCA mutation, who have been receiving talazoparib therapy in 6 medical centers of Russia since April 2021. Talazoparib was given at the standard dose 1 mg once daily, the dose was reduced, if any adverse event developed. Results . The median age of the patients was 50 years. 23 patients had a BRCA1 mutation, 5 patients had a BRCA2 mutation and one of the patients had a PALB2 mutation. Prior to starting talazoparib therapy, patients had received up to 9 lines of therapy for metastatic disease, the median was 1 line. The median follow-up period at that time was only 4.6 months. The median recurrence-free survival (RFS) was not reached. Progression was observed in 10 patients with a treatment period of 1 to 7.5 months, 19 patients continued to receive PARP inhibitor therapy without signs of disease progression, with a treatment period of 2 to 18 months. The objective response rate (ORR) was 57.2%, the clinical efficacy was confirmed in 85.7% of cases. The subgroup analysis showed that the lowest efficacy of therapy was reported in the group of patients, who had received prior therapy with platinum-based drugs, the median progression-free time (mPFT) was 4.5 months. (95% CI: 1.79-9.2). While for patients who had not received the prior platinum drug regimens, the median was not reached. Haematologic toxicities were common adverse events (AEs) for the talazoparib therapy, which were reported in 34.5% of cases. Transfusions of blood components were required in 3 patients, one of them required them repeatedly. All dose modifications were due to hematological toxicities. 7 patients (24.1%) required a dose reduction and 3 patients (10.3%) - repeated dose reduction. Conclusions . Testing for BRCA1/2 mutations in Her2-negative mBC should be a mandatory diagnostic procedure. Talazoparib therapy is an effective and safe treatment option for patients with gBRCAmut HER2-mBC.

Metastatic breast cancer (MBC) is an incurable disease by now. The main goals of treatment are prolongation of life, control of symptoms and preservation/improvement of quality of life. The modern arsenal of antitumor agents when choosing the optimal treatment regimen allows to be guided not only by efficiency and safety values, but also to take into account the ease of using drugs. Thus, the oral form of vinorelbine demonstrates high antitumor efficacy regardless of the subtype of breast cancer and the line of treatment, and also allows the patient to avoid serious toxicity and lead a regular lifestyle. This overview presents the results of the main clinical studies of vinorelbin, with special attention to combinations for the treatment of HER2-positive metastatic breast cancer. A case of successful treatment of a rare pathology – metastatic HER2-positive breast cancer in a man is presented.

The widespread introduction of anti-HER2 agents has changed the natural course of Her2-positive breast cancer. The use of trastuzumab, and later dual anti-HER2 blockade with pertuzumab, in neoadjuvant regimens significantly increased the chances of complete cure. However, among patients with early and locally advanced forms of Her2-positive cancer, there is a cohort with an extremely unfavorable prognosis – tumors that have not achieved complete pathomorphological regression after neoadjuvant chemotherapy.The presence of a residual tumor in Her2-positive breast cancer has long been only a prognostically unfavorable factor without the potential to influence disease outcome. The results of the international phase III study KATHERINE, which demonstrated the high efficacy of post-adjuvant therapy with trastuzumab emtansine (T-DM1) in this patient cohort, have established a new standard of care. Due to T-DM1 adjuvant therapy, the possibility to significantly improve long-term results determined the predictive characteristics of the morphological response to the choice of treatment tactics, which became an important argument in favor of neoadjuvant therapy in patients with not only locally advanced but also primarily resectable Her2-positive breast cancer, followed by personalization of therapy.This article presents our own experience with post-neoadjuvant therapy with trastuzumab emtansine in a young patient with a residual tumor. The data of the main studies in early Her2-positive breast cancer are summarized.

Understanding of cancer biology is at the cornerstone of design of new and effective treatment strategies. Identification of molecular drivers of tumor growth and progression allow identify right patient for the right treatment for personalized treatment plan optimization. Breast cancer (BC) encompasses a heterogeneous collection of neoplasms with diverse morphologies, molecular phenotypes, responses to therapy, probabilities of relapse and overall survival. Molecular and histopathological classification aims to categories tumors into subgroups to inform clinical decisions, to improve long-term treatment results and maintain the quality of life of this group of patients. Germinal mutation in the BRCA1/2 (BRCAm) genes in a tumor determines the hereditary predisposition, disease manifestation, therapeutic options and clinical efficacy. Therefore, patients withBRCAmBCrepresent a special subgroup requiring personalized treatment approach.Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is a targeted therapeutic agent that acts as inhibitor of single-strand breaks reparation, leading to their accumulation, conversion to double-strand breaks and eventually to cancer cell apoptosis. Olaparib is a first-in-class PARP-inhibitor with an outstanding antineoplastic activity known for some malignant tumors, demonstrates effectiveness and safety of therapy inBRCAmBCas well. The results of OlympiAD and LUCY trials are represented in the article. Subgroup analysis may define the patient population that would benefit from PARP inhibitors therapy.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors palbociclib, ribociclib and abemaciclib are the new treatment options for postmenopausal women with locally advanced or metastatic hormone-receptor (HR) positive human epidermal growth factor receptor 2 (HER2) negative BC. The aim of the current study is to conduct complex pharmacoeconomic evaluation of using CDK4/6 inhibitors palbociclib and ribociclib that are included in Vital and Essential Drug List (VEDL) in combination with letrozole in first line treatment from the Russian healthcare system prospective. Methods . Pharmacoeconomic evaluation consisted of two parts: clinical and economic study and budget impact analysis. We used cost minimization method for the clinical and economic study, since palbociclib and ribociclib are equally or comparably effective, according to earlier literature. Time horizon of clinical and economic study was 5 years. Direct medical costs including medications and adverse event treatments were considered. We accounted for treatment discontinuation and CDK4/6 inhibitors dose modifications. Budget impact analysis was performed for the three-year period of 2020-2022. All patients who can be treated with palbociclib or ribociclib were considered. Results . Mean direct medical costs of using palbociclib + letrozole were 2 082 333 RUB per patient, which were 505 016 RUB or 19.5% lower, compared to ribociclib + letrozole. According to current trends of BC morbidity, 8 098-8 221 newly diagnosed patients will be ready to start treatment with CDK4/6 inhibitors in 2020-2022 in Russia annually. Using palbociclib in this patient population lowers 3-year budget costs by 9 087 million RUB or by 22.5%, compared to ribociclib. Conclusions . Using palbociclib is the cost-saving treatment option for postmenopausal women with locally advanced or metastatic HR-positive HER2-negative BC, compared to ribociclib.

Introduction. The presence of a germinal BRCA mutation occurs in 3–4% of all breast cancer (BC) patients with various biological subtypes, but significantly with a high frequency in patients with a triple negative biological subtype (in 10–20% of cases). For the treatment of patients with HER2-negative metastatic breast cancer associated with gBRCA mutation, the effectiveness of biologically targeted drugs from the group of PARP inhibitors (olaparib and talazoparib) has been proven.Purpose. Comparison of the results of our experience with the use of talazoparib in patients with HER2-gBRCA+ + mBC with the data of the EMBRACA registration study.Materials and methods. As part of the multicenter compassionate use program (CUP) with the support of Pfizer, 24 patients with HER2-negative metastatic gBRCA-associated mutation metastatic breast cancer (HER2-gBRCA+ breast cancer) received biologically targeted therapy with the PARP inhibitor talazoparib at a standard oral dose of 1 mg per day for vital indications . The average age of patients with HER2-gBRCAm+ breast cancer was 50 years (29–90 years).Results. Objective response (OR) was registered in 29% of cases, disease control (OR+stabilization) – in 71% of cases. The median progression-free survival (PFS) was 6.5 months (95% CI [3–10]). Objective response, disease control, and median PFS were evaluated depending on the biological subtype, the number of lines of previous therapy, and the presence of platinum-containing agents in the anamnesis.Objective response and disease control were evaluated depending on the biological subtype: in patients with ER+HER2-mBC versus patients with triple negative subtype, OR was 33% vs 22%, and disease control was 83% vs 61%, respectively. In the presence of < 3 vs ≥ 3 lines of therapy for metastatic disease in the anamnesis, OR was 31% vs 12.5%, disease control – 75% vs 50% of cases, respectively. In the presence or absence of platinum-containing agents in the anamnesis, OR was observed in 22% vs 33% of cases, and disease control – 67% vs 67%, respectively.In patients with the luminal subtype versus patients with the triple negative subtype, the PFS was 9 months vs 5 months, respectively (HR = 0.705; 95% CI [0.231–2.147]; p = 0.5208). Median PFS in the presence of <3 vs ≥3 lines of therapy for metastatic disease in the anamnesis was 9 months vs 4 months, respectively (HR = 4,216; 95% CI [1,334–13,327]; p = 0.0056). In the presence or absence of platinum-containing agents in previous lines of therapy 5 months vs 9.5 months, respectively (HR =1.484; 95% CI [0.48–4.582]; p = 0.4750).During the treatment with talazoparib adverse events of the 3rd-4th grades were observed in 5 patients (20,8%). These include moderate and severe anemia in 3 patients (12.5%), thrombocytopenia in 1 patient (4%), and neutropenia in 1 patient (4%). The majority of patients (79,5%), which received talazoparib, did not require dose adjustment. The need to reduce the dose to 0.75 mg was noted in 3 patients (12.5%), to 0.5 mg – in 2 patients (8%). Hemotransfusion was performed in 3 patients. For effective therapy safety management regular monitoring of blood parameters is necessary.Conclusion. Thus, targeted therapy with talazoparib is an effective treatment option for HER2-gBRCA+ mBC.

Background. Treatment results for the patients with stage II–III triple negative breast cancer (TN BC) have to be improved. Not only the new treatment regimens, but new predictive and prognostic factors should to be developed.Materials and methods. We included 98 patients with stage II–III TN BC in our study. We studied efficacy and safety of PlaTax regimen (cisplatin 75 mg / m2 day 1 + paclitaxel 80 mg / m2 days 1, 8, 15, course every 4 weeks) in this cohort of patients. We assessed pathologic response, survival and factors, which were relevant for predicting response and prognose survival.Results. PlaTax regimen is characterized by high efficacy and tolerable toxicity. Clinical efficacy was 85.8 %, pCR achievement was 60.5 %, tpCR achievement was 58.1 %. The regimen has low haematological toxicity (neutropenia III–IV grades – 4.1 %); the most frequent adverse events were polyneuropathy (18.5 %) and decreased renal function (24.5 %). 3-year progression-free survival was 68.4 %, most of the relapses (92 %) occurred during first 2 years. 3 year overall survival was 77.6 %. The most relevant predictive factor was level of Ki-67 ≥50 % (pCR 38.5 % vs. 68.7 %, p = 0.038). pCR achievement was the most important prognostic factor, resulting in improved 3-year progressionfree survival (44.3 % vs. 89.1 %, p <0.0001), and 3-year overall survival (61.5 % vs. 91.6 %, p = 0.001). Not only the residual disease, but also the size of residual tumor was important from prognostic point of view. Other important prognostic factors were size of the tumor, status of regional lymph nodes, grade. Delay in surgical treatment more than a month lead to decreased 3-year progression-free survival: 87.1 % vs. 62.5 % (p = 0.047).Conclusions. Our data suggest that studied regimen could be an option for patients with stage II–III TN BC. The assessment of the predictive and prognostic factors will help improve the treatment results for patients with stage II–III TN BC.

Understanding of cancer biology is at the cornerstone of design of new and effective treatment strategies. Identification of molecular drivers of tumor growth and progression allow identify right patient for the right treatment for personalized treatment plan optimization. Breast cancer (BC) encompasses a heterogeneous collection of neoplasms with diverse morphologies, molecular phenotypes, responses to therapy, probabilities of relapse and overall survival. Molecular and histopathological classification aims to categories tumors into subgroups to inform clinical decisions, to improve long-term treatment results and maintain the quality of life of this group of patients. Germinal mutation in the BRCA1/2 (BRCAm) genes in a tumor determines the hereditary predisposition, disease manifestation, therapeutic options and clinical efficacy. Therefore, patients withBRCAmBCrepresent a special subgroup requiring personalized treatment approach. Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is a targeted therapeutic agent that acts as inhibitor of single-strand breaks reparation, leading to their accumulation, conversion to double-strand breaks and eventually to cancer cell apoptosis. Olaparib is a first-in-class PARP-inhibitor with an outstanding antineoplastic activity known for some malignant tumors, demonstrates effectiveness and safety of therapy inBRCAmBCas well. The results of OlympiAD and LUCY trials are represented in the article. Subgroup analysis may define the patient population that would benefit from PARP inhibitors therapy.

Breast cancer steadily holds leading market positions in the malignancy morbidity and mortality pattern. The treatment of metastatic breast cancer remains an extremely topical issue, when its aim is not only to prolong the patient’s life, but also to preserve its quality. Due to advances in molecular diagnostics, it has become possible to use several new classes of drugs in recent times. CDK4/6 inhibitors that demonstrate high efficacy in the first-line therapy for luminal metastatic breast cancer is one of these groups. This review presents data from recent registration studies and a description of observations from our own clinical experience.

Breast cancer steadily holds leading market positions in the malignancy morbidity and mortality pattern. The treatment of metastatic breast cancer remains an extremely topical issue, when its aim is not only to prolong the patient’s life, but also to preserve its quality. Due to advances in molecular diagnostics, it has become possible to use several new classes of drugs in recent times. CDK4/6 inhibitors that demonstrate high efficacy in the first-line therapy for luminal metastatic breast cancer is one of these groups. This review presents data from recent registration studies and a description of observations from our own clinical experience.