Results of organ-preserving treatment of breast cancer using intraoperative radial therapy

Objective: to compare the immediate and long-term outcomes of patients with early breast cancer treated with intraoperative radial therapy depending on the biological subtype of breast cancer.Materials and methods. We prospectively evaluated number of recurrences, cosmetic effect and early treatment results of 104 patients with early breast cancer aged 66.72 ± 0.68 years old. The mean follow-up period was 36 months. The mean dose on the surface of applicator was 17.8 Gy, on the depth 0.5 cm – 8.8 Gy, on the depth 1.0 cm – 5 Gy. The mean time of radiation was 22.15 min ± 28.09 sec.Results. The local recurrence was in 3 patients. The first patient had triple negative breast cancer subtype, the second patient had luminal B HER2+, and the third one had luminal B HER2– subtype. Relapses occurred in 7, 14 and 20 months after the end of treatment respectively. The recurrence rate in patients with luminal B biological subtype was 10.71 %; in patients with triple negative subtype was 20 %. All recurrences were found in the area of the postoperative scar.Conclusion. The obtained results question the rationale for the use of the demonstrated method in patients with luminal B and triple negative molecular subtypes of tumors.

Prognostic role of clinical and biological factors and parameters of hormonal profile in patients with primary inoperable HER2-negative breast cancer

Relevance. Breast cancer (BC) is among the most common cancers and the leading causes of cancer death in women worldwide. Much attention is paid to the problem of its hormoneresistance; however, the issues of using prognostic markers and predictors in routine cancer clinical practice remain unresolved. Aim. Study and analysis of prognostic significance of clinical and biological factors and parameters of the hormonal profile in patients with primary inoperable HER2-negative breast cancer receiving neoadjuvant chemotherapy. Materials and methods. The study included 162 patients with locally advanced primary inoperable HER2-negative breast cancer. Patients were divided into 2 groups. Group 1 included 58 patients with early disease progression within 6 to 12 months after radical surgical treatment. Group 2 included 104 patients with no disease progression within 2 years after radical surgical treatment. In all cases, diagnosis was verified histologically and immunohistochemically. Levels of prolactine, progesterone, estradiol, luteinizing hormone (LH), follicle-stimulating hormone, testosterone and cortisol were measured by RIA. The blood plasma values in 20 healthy donors were used as reference one. The data were processed using the Statistica 7.0 and MedCalc (version 9.3.5.0) programs. All patients received combination antitumor treatment according to clinical guidance. Results. An analysis of the overall (OS) and event-free (EFS) survival in group 1 showed that the median EFS in patients with luminal B BC was 9 months, with triple-negative BC (TNBC) 8 months. 6-month EFS in luminal B subtype was 87.5%, in TNBC 79.4%, p=0.37985. 1-year EFS was 1.721.7% regardless of the biological subtype. The median OS in luminal B BC was 25 months, in TNBC 26 months. 1-year OS in luminal B BC 100%, in TNBC 93.9%, p=0.138. 2-year OS in luminal B BC 54.2%, in TNBC 55.9%, p=0.697. 3-year survival in luminal B BC 37.5%, in TNBC 41.2%, p=0.639. An analysis of OS and EFS in group 2 showed that the median EFS was not reached for all biological subtypes. 3-year survival in the group was 100% regardless of the biological subtype. The median OS was not reached for all biological subtypes. 3-year OS in the group was 100%. An analysis of the hormonal profile in the treatment dynamics showed decreased levels of estradiol in all groups of patients (by 1.6 times). In group 1, progesterone was decreased by 2.1 times, testosterone by 2.4 times and LH by 2.1 times in all BC subtypes (p0.05). Patients of group 2 showed 2 times reduced cortisol and 3 times reduced prolactin in all BC subtypes, while LH levels were elevated by 1.6 times in luminal A and B BC. Conclusion. Aggressive course was observed similarly in triple-negative cancer as well as in luminal cancer with primary hormone resistance. Studying of pituitary and sex hormones and cortisol have a great clinical significance in patients with all biological subtypes of BC. This should be taken into account when predicting the course of the disease and developing further treatment options.

Age-Related Features of the Distribution of the Frequency of Occurrence of Luminal A Molecular-Biological Subtype of Breast Cancer

Aim. In this article, we analyzed the age-related features of molecular- biological subtypes in 499 patients with invasive breast cancer. Materials and research methods. All cases were divided into 5 molecular- biological subtypes based on immunohistochemical studies of hormone receptors, Her2, Ki-67. Luminal (A and B) with the expression of estrogen and/or progesterone receptors (ER+/PR+), accounting for about 50-80% of all breast cancer cases and potentially sensitive, especially luminal A, to hormone therapy. Research results. The analysis showed that in our study the proportion of the Luminal A subtype was lower than the generally accepted values of 37.4% of all studied breast cancer cases. In the group of women under 40 years of age (with preserved menstrual-ovarian function), cases of Luminal A subtype were significantly less common (9.03%) compared to the groups of 41-50 years (p<0.006), 51-60 years (p<0.001), and over 60 (p<0.001). There was also a decrease in the proportion of Luminal A subtype among patients older than 60 years (p=0.0064). No significant differences were found between the groups 41-50 and over 60 years of age (p=0.1868).

Russian multicenter experience of using talazoparib in the treatment of patients with BRCA-associated metastatic breast cancer

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.

Strategy of post-neoadjuvant treatment of patients with residual breast cancer

The article considers the aspects of selection of post-neoadjuvant therapy for patients with residual breast cancer depending on biological subtype and molecular profile of the tumor. Analysis of morphological and molecular markers allowing to evaluate sensitivity of malignant breast tumors with high recurrence risk to new types of systemic treatment is presented.