PURPOSE: Resistance to endocrine therapy poses a major clinical challenge for patients with hormone receptor-positive (HR +), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). We present the preplanned 24-month final overall survival (OS) results, alongside updated progression-free survival (PFS), and objective response rate (ORR) results. METHODS: nextMONARCH is an open-label, controlled, randomized, Phase 2 study of abemaciclib alone or in combination with tamoxifen in women with endocrine-refractory HR + , HER2- MBC previously treated with chemotherapy. Patients were randomized 1:1:1 to: abemaciclib 150 mg and tamoxifen 20 mg (A + T), abemaciclib 150 mg (A-150), or abemaciclib 200 mg and prophylactic loperamide (A-200). OS was the main prespecified secondary endpoint. PFS, ORR, and safety at 24 months were compared to previously reported primary analysis results. RESULTS: Of the 234 patients enrolled, 12 were receiving study treatment at data cutoff (28Jun2019). Median follow-up was 27.2 months. Median OS was 24.2 months in the A + T arm, 20.8 months in A-150, and 17.0 months in A-200 (A + T versus A-200: HR 0.62; 95%CI [0.40, 0.97], P = 0.03 and A-150 versus A-200: HR 0.96; 95%CI [0.64, 1.44], P = 0.83). PFS and ORR results at 24 months were consistent with the primary analysis. The safety profile corresponded with previous reports. CONCLUSION: The addition of tamoxifen to abemaciclib demonstrated greater OS benefit than monotherapy. This study confirmed the single-agent activity of abemaciclib in heavily pretreated women with endocrine-refractory HR + , HER2- MBC, as well as the previously reported primary PFS and ORR results, with no new safety signals observed. Trial Registration ClinicalTrials.gov Identifier: NCT02747004.

• Klíčová slova
• Cyclin-dependent kinase 4 and 6, Endocrine therapy, HER2-negative, Hormone receptor-positive, MBC, Overall survival,
• MeSH
• aminopyridiny * škodlivé účinky   MeSH
• benzimidazoly * škodlivé účinky   MeSH
• doba přežití bez progrese choroby MeSH
• lidé MeSH
• nádory prsu * farmakoterapie   patologie   MeSH
• protokoly antitumorózní kombinované chemoterapie * škodlivé účinky   MeSH
• tamoxifen terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• abemaciclib MeSH Prohlížeč
• aminopyridiny * MeSH
• benzimidazoly * MeSH
• tamoxifen MeSH

PURPOSE: CompLEEment-1 (NCT02941926) is a single-arm, open-label, multicentre phase IIIb study investigating the safety and efficacy of ribociclib plus letrozole (RIB + LET) in a large, diverse cohort who have not received prior endocrine therapy (ET) for advanced disease. We present an exploratory analysis of male patients. METHODS: Eligible patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), who had no prior ET and ≤ 1 line of prior chemotherapy for advanced disease, received RIB + LET. Male patients also received goserelin or leuprolide. Primary endpoint was safety and tolerability; efficacy was a secondary endpoint. RESULTS: In total, 39/3246 patients were male. Baseline characteristics were similar to the overall population. Male patients experienced fewer treatment-related adverse events (AEs) and treatment-related serious AEs compared with the overall population; fewer male patients had treatment-related AEs leading to discontinuation, adjustment/interruption, or additional therapy. One male patient died as a result of a serious AE that was not considered to be treatment-related. The most common AE was neutropenia; the incidence of grade ≥ 3 neutropenia in males (41.0%) was lower than in the overall population (57.2%). Median follow-up was 25.4 months; median time to progression was not reached in males versus 27.1 months for the overall population. CONCLUSION: The clinical benefit and overall response rates in males were consistent with the overall population. This analysis demonstrates the safety and efficacy of ribociclib in a close-to-real-world setting, supporting the use of RIB + LET in male patients with HR+, HER2- ABC. TRIAL REGISTRATION NUMBER: NCT02941926 (Registered 2016).

• Klíčová slova
• Advanced breast cancer, Male breast cancer, Men, Real-world evidence, Ribociclib,
• MeSH
• aminopyridiny MeSH
• letrozol terapeutické užití   MeSH
• lidé MeSH
• nádory prsu u mužů * farmakoterapie   MeSH
• neutropenie farmakoterapie   etiologie   MeSH
• protokoly antitumorózní kombinované chemoterapie * škodlivé účinky   MeSH
• puriny MeSH
• receptor erbB-2 genetika   metabolismus   MeSH
• receptory pro estrogeny metabolismus   MeSH
• receptory progesteronu metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• Názvy látek
• aminopyridiny MeSH
• ERBB2 protein, human MeSH Prohlížeč
• letrozol MeSH
• puriny MeSH
• receptor erbB-2 MeSH
• receptory pro estrogeny MeSH
• receptory progesteronu MeSH
• ribociclib MeSH Prohlížeč

PURPOSE: CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer cancer stem cells (CSC). Reparixin (R), an investigational oral inhibitor of CXCR1, was safely administered to metastatic breast cancer patients in combination with paclitaxel (P) and appeared to reduce CSC in a window-of-opportunity trial in operable breast cancer. The fRida trial (NCT02370238) evaluated the addition of R to weekly as first-line therapy for metastatic (m) TNBC. SUBJECTS AND METHODS: Subjects with untreated mTNBC were randomized 1:1 to R or placebo days 1-21 in combination with weekly P 80 mg/m2 on days 1, 8, 15 of 28-day cycles. The primary endpoint was PFS by central review. RESULTS: 123 subjects were randomized (62 to R + P and 61 to placebo + P). PFS was not different between the 2 groups (median 5.5 and 5.6 months for R + P and placebo + P, respectively; HR 1.13, p = 0.5996). ALDH+ and CD24-/CD44+ CSC centrally evaluated by IHC were found in 16 and 34 of the 54 subjects who provided a metastatic tissue biopsy at study entry. Serious adverse events (21.3 and 20% of subjects) and grade ≥ 3 adverse reactions (ADR) (9.1 and 6.3% of all ADRs) occurred at similar frequency in both groups. CONCLUSION: fRida is the first randomized, double-blind clinical trial of a CSC-targeting agent in combination with chemotherapy in breast cancer. The primary endpoint of prolonged PFS was not met. CLINICAL TRIAL REGISTRATION/DATE OF REGISTRATION: NCT01861054/February 24, 2015.

• Klíčová slova
• CXCR1, Cancer stem cells, Reparixin, TNBC,
• MeSH
• lidé MeSH
• paclitaxel škodlivé účinky   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• sulfonamidy MeSH
• triple-negativní karcinom prsu * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• paclitaxel MeSH
• reparixin MeSH Prohlížeč
• sulfonamidy MeSH

PURPOSE: For optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk. METHODS: Using a case-cohort design, reliability was assessed in a population-based, nationwide cohort of 2767 women with screen-detected DCIS diagnosed between 1993 and 2004, treated by breast-conserving surgery with/without radiotherapy (BCS ± RT) using Krippendorff's alpha (KA) and Gwet's AC2 (GAC2). Thirty-eight raters scored histopathological DCIS features including grade (2-tiered and 3-tiered), growth pattern, mitotic activity, periductal fibrosis, and lymphocytic infiltrate in 342 women. Using majority opinion-based scores for each feature, their association with subsequent iIBC risk was assessed using Cox regression. RESULTS: Interrater reliability of grade using various classifications was fair to moderate, and only substantial for grade 1 versus 2 + 3 when using GAC2 (0.78). Reliability for growth pattern (KA 0.44, GAC2 0.78), calcifications (KA 0.49, GAC2 0.70) and necrosis (KA 0.47, GAC2 0.70) was moderate using KA and substantial using GAC2; for (type of) periductal fibrosis and lymphocytic infiltrate fair to moderate estimates were found and for mitotic activity reliability was substantial using GAC2 (0.70). Only in patients treated with BCS-RT, high mitotic activity was associated with a higher iIBC risk in univariable analysis (Hazard Ratio (HR) 2.53, 95% Confidence Interval (95% CI) 1.05-6.11); grade 3 versus 1 + 2 (HR 2.64, 95% CI 1.35-5.14) and a cribriform/solid versus flat epithelial atypia/clinging/(micro)papillary growth pattern (HR 3.70, 95% CI 1.34-10.23) were independently associated with a higher iIBC risk. CONCLUSIONS: Using majority opinion-based scores, DCIS grade, growth pattern, and mitotic activity are associated with iIBC risk in patients treated with BCS-RT, but interrater variability is substantial. Semi-quantitative grading, incorporating and separately evaluating nuclear pleomorphism, growth pattern, and mitotic activity, may improve the reliability and prognostic value of these features.

• Klíčová slova
• Ductal carcinoma in situ, Interrater reliability, Invasive breast cancer, Risk stratification,
• MeSH
• duktální karcinom prsu * chirurgie   MeSH
• intraduktální neinfiltrující karcinom * chirurgie   MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• nádory prsu * chirurgie   MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• segmentální mastektomie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• faktor stimulující kolonie granulocytů MeSH
• lidé MeSH
• nádory prsu * MeSH
• neutrofily * MeSH
• průtoková cytometrie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• Názvy látek
• faktor stimulující kolonie granulocytů MeSH

PURPOSE: Nuclear grade is an important indicator of the biological behaviour of ductal carcinoma in situ (DCIS). De-escalation of treatment has been suggested for low-grade DCIS. Our aim is to estimate the relative rate of progression of DCIS by nuclear grade by analysing the distribution of nuclear grade by detection at initial or subsequent screening. METHODS: We asked International Cancer Screening Network sites to complete, based on their screening and clinical databases, an aggregated data file on DCIS detection, diagnosis and treatment. RESULTS: Eleven screening programs reported 5068 screen-detected pure DCIS in nearly 7 million screening tests in women 50-69 years of age. For all programs combined, low-grade DCIS were 20.1% (range 11.4-31.8%) of graded DCIS, intermediate grade 31.0% and high grade 48.9%. Detection rates decreased more steeply from initial to subsequent screening in low compared to high-grade DCIS: the ratios of subsequent to initial detection rates were 0.39 for low grade, 0.51 for intermediate grade, and 0.75 for high grade (p < 0.001). CONCLUSIONS: These results suggest that the duration of the preclinical detectable phase is longer for low than for high-grade DCIS. The findings from this large multi-centre, international study emphasize that the management of low-grade DCIS should be carefully scrutinized in order to minimize overtreatment of screen-detected slow-growing or indolent lesions. The high variation by site in the proportion of low grade suggests that further pathology standardization and training would be beneficial.

• Klíčová slova
• Breast cancer screening, Ductal carcinoma in situ, Low-grade DCIS, Overtreatment,
• MeSH
• časná detekce nádoru MeSH
• intraduktální neinfiltrující karcinom diagnóza   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu diagnóza   epidemiologie   MeSH
• plošný screening MeSH
• progrese nemoci MeSH
• senioři MeSH
• staging nádorů MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Spojené státy americké epidemiologie   MeSH

BACKGROUND: Several studies have demonstrated a prognostic role for stromal tumour infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC). The reproducibility of scoring sTILs is variable with potentially excellent concordance being achievable using a software tool. We examined agreement between breast pathologists across Europe scoring sTILs on H&E-stained sections without software, an approach that is easily applied in clinical practice. The association between sTILs and response to anthracycline-taxane NACT was also examined. METHODOLOGY: Pathologists from the European Working Group for Breast Screening Pathology scored sTILs in 84 slides from 75 TNBCs using the immune-oncology biomarker working group guidance in two circulations. There were 16 participants in the first and 19 in the second circulation. RESULTS: Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601-0.767, p-value < 0.001). Agreement was less when a 25% threshold was used (ICC 0.509, 95% CI 0.416-0.614, p-value < 0.001) and for lymphocyte predominant breast cancer (LPBC) (ICC 0.504, 95% CI 0.412-0.610, p-value < 0.001). Intra-observer agreement was strong for absolute sTIL values (Spearman ρ = 0.727); fair for sTILs ≥ 25% (κ = 0.53) and for LPBC (κ = 0.49), but poor for sTILs as 10% increments (κ = 0.24). Increasing sTILs was significantly associated with an increased likelihood of a pathological complete response (pCR) on multivariable analysis. CONCLUSION: Increasing sTILs in TNBCs improves the likelihood of a pCR. However, inter-observer agreement is such that H&E-based assessment is not sufficiently reproducible for clinical application. Other methodologies should be explored, but may be at the cost of ease of application.

• Klíčová slova
• Inter-observer agreement, Neoadjuvant chemotherapy, Pathological complete response, Stromal tumour infiltrating lymphocytes, Triple-negative breast cancer, sTILs,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádorové biomarkery MeSH
• nádorové mikroprostředí MeSH
• neoadjuvantní terapie MeSH
• odchylka pozorovatele MeSH
• odds ratio MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• staging nádorů MeSH
• stupeň nádoru MeSH
• triple-negativní karcinom prsu diagnóza   imunologie   terapie   MeSH
• tumor infiltrující lymfocyty patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• multicentrická studie MeSH
• úvodníky MeSH
• Názvy látek
• nádorové biomarkery MeSH

PURPOSE: The phase 3 MONALEESA-2 study demonstrated that addition of ribociclib (RIB) to letrozole (LET) significantly improved progression-free survival (PFS) in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). Here, we evaluated duration of response (DoR), tumor shrinkage, PFS by treatment-free interval (TFI), and health-related quality of life (HRQoL). METHODS: Postmenopausal women (N = 668) with HR+ , HER2- ABC and no prior systemic therapy for ABC were randomized to RIB (600 mg/day; 3 weeks on/1 week off) plus LET (2.5 mg/day; continuous) or placebo (PBO) plus LET. Primary end point was PFS; HRQoL was the secondary end point; DoR was exploratory end point and PFS by TFI was post hoc analysis. RESULTS: Of 501 pts with measurable disease and confirmed complete or partial response, median DoR was 26.7 months (95% CI, 24.0-NR) in the RIB arm versus 18.6 months (95% CI, 14.8-23.1) in the PBO arm. At 8 weeks, more pts in the RIB arm (32%) versus the PBO arm (17%) experienced best percentage change ≥ 60%. The average pain reduction was greater in the RIB arm (26%) versus the PBO arm (15%). PFS benefit was seen with RIB vs PBO, irrespective of TFI. CONCLUSION: RIB plus LET versus PBO plus LET is associated with earlier and more durable tumor response, greater degree of tumor shrinkage and pain reduction, and PFS benefit irrespective of TFI. These data further support RIB plus LET as a first-line treatment option for postmenopausal women with HR+ , HER2- ABC.

• Klíčová slova
• Advanced breast cancer, CDK4/6, MONALEESA-2, Ribociclib,
• MeSH
• aminopyridiny aplikace a dávkování   MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• kvalita života MeSH
• letrozol aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• mladý dospělý MeSH
• nádorové biomarkery MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• puriny aplikace a dávkování   MeSH
• receptor erbB-2 metabolismus   MeSH
• receptory pro estrogeny metabolismus   MeSH
• receptory progesteronu metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• aminopyridiny MeSH
• letrozol MeSH
• nádorové biomarkery MeSH
• puriny MeSH
• receptor erbB-2 MeSH
• receptory pro estrogeny MeSH
• receptory progesteronu MeSH
• ribociclib MeSH Prohlížeč

PURPOSE: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. METHODS: In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). RESULTS: A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). CONCLUSION: Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.

• Klíčová slova
• Avelumab, Metastatic breast cancer, PD-L1, Second-line, Triple-negative breast cancer,
• MeSH
• antigeny CD274 antagonisté a inhibitory   genetika   imunologie   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   imunologie   patologie   MeSH
• metastázy nádorů MeSH
• monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• protilátky anti-idiotypické aplikace a dávkování   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• senioři MeSH
• triple-negativní karcinom prsu farmakoterapie   genetika   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antigeny CD274 MeSH
• avelumab MeSH Prohlížeč
• CD274 protein, human MeSH Prohlížeč
• humanizované monoklonální protilátky MeSH
• monoklonální protilátky MeSH
• protilátky anti-idiotypické MeSH

PURPOSE: Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. METHODS: Postmenopausal women with HR+ , HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. RESULTS: Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27-0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. CONCLUSIONS: Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2- de novo advanced breast cancer.

• Klíčová slova
• Breast cancer, CDK inhibitor, De novo advanced breast cancer, Endocrine therapy, Hormone receptor-positive, Ribociclib,
• MeSH
• aminopyridiny terapeutické užití   MeSH
• časové faktory MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• febrilní neutropenie vyvolaná chemoterapií epidemiologie   etiologie   MeSH
• incidence MeSH
• Kaplanův-Meierův odhad MeSH
• kritéria léčebné odpovědi MeSH
• letrozol terapeutické užití   MeSH
• leukopenie chemicky indukované   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu farmakoterapie   mortalita   patologie   MeSH
• postmenopauza MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• prsy patologie   MeSH
• puriny terapeutické užití   MeSH
• receptory pro estrogeny metabolismus   MeSH
• receptory progesteronu metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• aminopyridiny MeSH
• letrozol MeSH
• puriny MeSH
• receptory pro estrogeny MeSH
• receptory progesteronu MeSH
• ribociclib MeSH Prohlížeč