Oxygenated metabolites of cholesterol (oxysterols) have been previously demonstrated to contribute to progression of various cancers and to modulate resistance to breast cancer endocrine therapy in vitro. We measured prognostic roles of circulating levels of seven major oxysterols in the progression of luminal subtype breast carcinoma. Liquid chromatography coupled with tandem mass spectrometry was used for determination of levels of non-esterified 25-hydroxycholesterol, 27-hydroxycholesterol, 7α-hydroxycholesterol, 7-ketocholesterol, cholesterol-5α,6α-epoxide, cholesterol-5β,6β-epoxide, and cholestane-3β,5α,6β-triol in plasma samples collected from patients (n = 58) before surgical removal of tumors. Oxysterol levels were then associated with clinical data of patients. All oxysterols except cholesterol-5α,6α-epoxide were detected in patient plasma samples. Circulating levels of 7α-hydroxycholesterol and 27-hydroxycholesterol were significantly lower in patients with small tumors (pT1) and cholesterol-5β,6β-epoxide and cholestane-3β,5α,6β-triol were lower in patients with stage IA disease compared to larger tumors or more advanced stages. Patients with higher than median cholestane-3β,5α,6β-triol levels had significantly worse disease-free survival than patients with lower levels (p = 0.037 for all patients and p = 0.015 for subgroup treated only with tamoxifen). In conclusion, this study shows, for the first time, that circulating levels of oxysterols, especially cholestane-3β,5α,6β-triol, may have prognostic roles in patients with luminal subtype breast cancer.

• MeSH
• duktální karcinom prsu krev   patologie   MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádorové biomarkery analýza   MeSH
• nádory prsu krev   patologie   MeSH
• následné studie MeSH
• oxysteroly krev   MeSH
• prognóza MeSH
• receptor erbB-2 metabolismus   MeSH
• receptory pro estrogeny metabolismus   MeSH
• receptory progesteronu metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

OBJECTIVE: HER2 negative carcinomas of the breast pose a challenge for treatment due to redundancies in potential drug targets and poor patient outcomes. Our aim was to investigate the role of L-type amino acid transporter - LAT1 as a potential prognosticator and a drug target. METHODS: In this retrospective work, we have studied the expression of LAT1 in 145 breast cancer tissues via immunohistochemistry. Overall survival analysis was used to evaluate patient outcome in various groups of our cohort. RESULTS: Positive LAT1 expression was found in 27 (84.4%) luminal A subtype, 27 (64.3%) luminal B/triple positive subtype, 29 (82.9%) triple negative subtype, and 24 (66.7%) HER2-only positive subtype (p=0.1). Interestingly, negative correlation was found between LAT1 and HER2; where positive expression of LAT1 was found in 56 (83.6%) cases in negative HER2 group and 51 (65.4%) cases from positive HER2 group (p=0.01). Unfortunately, we were unable to report significant survival differences when LAT1 expression was studied in the negative HER2 group. Nevertheless, five incidents of mortality (out of 55) were reported in LAT1+/HER2- group compared to none in the LAT1-/HER2- group (N=11). CONCLUSION: Our findings of overexpression of LAT1 in negative HER2 group suggest a role of this protein as prognosticator and drug target in a challenging therapeutic cohort.
.

• MeSH
• dospělí MeSH
• duktální karcinom prsu metabolismus   patologie   chirurgie   MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• lobulární karcinom metabolismus   patologie   chirurgie   MeSH
• lokální recidiva nádoru metabolismus   patologie   chirurgie   MeSH
• lymfatické metastázy MeSH
• míra přežití MeSH
• nádorové biomarkery metabolismus   MeSH
• následné studie MeSH
• přenašeč velkých neutrálních aminokyselin 1 metabolismus   MeSH
• prognóza MeSH
• receptor erbB-2 metabolismus   MeSH
• receptory pro estrogeny metabolismus   MeSH
• receptory progesteronu metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• triple-negativní karcinom prsu metabolismus   patologie   chirurgie   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

BACKGROUND: Pleomorphic and Florid Lobular carcinoma in situ (P/F LCIS) are rare variants of LCIS, the exact nature of which is still debated. AIM: To collect a large series of P/F LCIS diagnosed on preoperative biopsies and evaluate their association with invasive carcinoma and high grade duct carcinoma in situ (DCIS). Data obtained were compared with those reported in the literature. METHODS: A multi-institutional series of P/F LCIS was retrieved. All cases were diagnosed on pre-operative biopsies, which was followed by an open surgical excision. Data on post-operative histopathology were available. A literature review was performed. RESULTS: A total of 117 cases were collected; invasive carcinoma and/or DCIS was present in 78/117 cases (66.7%). Seventy cases of P/F LCIS were pure on biopsy and 31 of these showed pathological upgrade in post-surgical specimens. Pre-operative biopsy accuracy was 47/78 (60.3%); pre-operative biopsy underestimation of cancer was 31/78 (39,7.%). In the literature review papers, invasive carcinoma or DCIS was associated with 274 of 418 (65.5%) cases of P/F LCIS. Pre-operative biopsy accuracy was 66% (181/274) whereas pre-operative biopsy underestimation of cancer was 33.9% (93/274). CONCLUSIONS: The data presented here indicate that P/F LCIS is frequently associated with invasive carcinoma or high grade DCIS and that pre-operative biopsy is associated with an underestimation of malignancy. Open surgery is indicated when P/F LCIS is diagnosed pre-operatively.

• MeSH
• biopsie MeSH
• dospělí MeSH
• duktální karcinom prsu patologie   chirurgie   MeSH
• intraduktální neinfiltrující karcinom patologie   chirurgie   MeSH
• invazivní růst nádoru MeSH
• karcinom prsu in situ patologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lobulární karcinom patologie   chirurgie   MeSH
• nádory prsu patologie   chirurgie   MeSH
• resekční okraje MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň nádoru 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
• multicentrická studie MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH

Multidrug resistance to anticancer drugs, which is often associated with enhanced expression of the ATP‑binding cassette (ABC) transporter P‑glycoprotein (encoded by the ABCB1 gene) may limit the effects of cancer therapy. Epigenetic regulation of ABCB1 expression may thus have a clinical impact. A detailed assessment of ABCB1 promoter methylation is of importance for predicting therapy outcome and prognosis. Thus, validated methods for the analysis of ABCB1 promoter methylation are urgently required. In the present study, high‑resolution melting (HRM) analysis of the CpG island regions covering the distal promoter of the ABCB1 gene was developed and compared with pyrosequencing. In addition, the clinical effects of the methylation status of the ABCB1 promoter were analyzed in patients with breast and ovarian carcinoma prior and subsequent to chemotherapy treatment. HRM analysis of ABCB1 methylation correlated with the results of pyrosequencing (P=0.001) demonstrating its analytical validity and utility. Hypermethylation of the analyzed ABCB1 promoter region was significantly correlated with low levels of the ABCB1 transcript in tumors from a subset of patients with breast and ovarian carcinoma prior to chemotherapy but not following treatment. Finally, high ABCB1 transcript levels were observed in tumors of patients with short progression‑free survival prior to chemotherapy. Our data suggest the existence of functional epigenetic changes in the ABCB1 gene with prognostic value in tumor tissues of patients with breast and ovarian carcinoma. The clinical importance of such changes should be further evaluated.

• MeSH
• denaturace nukleových kyselin MeSH
• duktální karcinom prsu farmakoterapie   genetika   patologie   MeSH
• epigeneze genetická MeSH
• invazivní růst nádoru MeSH
• lidé MeSH
• metylace DNA * MeSH
• míra přežití MeSH
• nádorové biomarkery genetika   MeSH
• nádory prsu farmakoterapie   genetika   patologie   MeSH
• nádory vaječníků farmakoterapie   genetika   patologie   MeSH
• následné studie MeSH
• P-glykoproteiny genetika   MeSH
• polymerázová řetězová reakce metody   MeSH
• prognóza MeSH
• promotorové oblasti (genetika) * MeSH
• regulace genové exprese u nádorů MeSH
• retrospektivní studie MeSH
• serózní cystadenokarcinom farmakoterapie   genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• bevacizumab terapeutické užití   MeSH
• dospělí MeSH
• duktální karcinom prsu * diagnóza   farmakoterapie   chirurgie   patologie   MeSH
• erbB receptory antagonisté a inhibitory   účinky léků   MeSH
• klinické rozhodování MeSH
• kojení MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory prsu * diagnóza   klasifikace   terapie   MeSH
• neoadjuvantní terapie MeSH
• prognóza MeSH
• protinádorové látky imunologicky aktivní klasifikace   terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie MeSH
• triple-negativní karcinom prsu farmakoterapie   chirurgie   komplikace   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• novinové články MeSH

• MeSH
• adjuvantní chemoterapie MeSH
• chemorezistence MeSH
• duktální karcinom prsu diagnóza   patologie   terapie   MeSH
• everolimus * škodlivé účinky   terapeutické užití   MeSH
• hypercholesterolemie chemicky indukované   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory jater farmakoterapie   sekundární   MeSH
• nádory kostí farmakoterapie   sekundární   MeSH
• nádory prsu * diagnóza   patologie   terapie   MeSH
• progrese nemoci MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: We previously confirmed the non-inferiority of accelerated partial breast irradiation (APBI) with interstitial brachytherapy in terms of local control and overall survival compared with whole-breast irradiation for patients with early-stage breast cancer who underwent breast-conserving surgery in a phase 3 randomised trial. Here, we present the 5-year late side-effects and cosmetic results of the trial. METHODS: We did this randomised, controlled, phase 3 trial at 16 centres in seven European countries. Women aged 40 years or older with stage 0-IIA breast cancer who underwent breast-conserving surgery with microscopically clear resection margins of at least 2 mm were randomly assigned 1:1, via an online interface, to receive either whole-breast irradiation of 50 Gy with a tumour-bed boost of 10 Gy or APBI with interstitial brachytherapy. Randomisation was stratified by study centre, menopausal status, and tumour type (invasive carcinoma vs ductal carcinoma in situ), with a block size of ten, according to an automated dynamic algorithm. Patients and investigators were not masked to treatment allocation. The primary endpoint of our initial analysis was ipsilateral local recurrence; here, we report the secondary endpoints of late side-effects and cosmesis. We analysed physician-scored late toxicities and patient-scored and physician-scored cosmetic results from the date of breast-conserving surgery to the date of onset of event. Analysis was done according to treatment received (as-treated population). This trial is registered with ClinicalTrials.gov, number NCT00402519. FINDINGS: Between April 20, 2004, and July 30, 2009, we randomly assigned 1328 women to receive either whole-breast irradiation (n=673) or APBI with interstitial brachytherapy (n=655); 1184 patients comprised the as-treated population (551 in the whole-breast irradiation group and 633 in the APBI group). At a median follow-up of 6·6 years (IQR 5·8-7·6), no patients had any grade 4 toxities, and three (<1%) of 484 patients in the APBI group and seven (2%) of 393 in the whole-breast irradiation group had grade 3 late skin toxicity (p=0·16). No patients in the APBI group and two (<1%) in the whole-breast irradiation group developed grade 3 late subcutaneous tissue toxicity (p=0·10). The cumulative incidence of any late side-effect of grade 2 or worse at 5 years was 27·0% (95% CI 23·0-30·9) in the whole-breast irradiation group versus 23·3% (19·9-26·8) in the APBI group (p=0·12). The cumulative incidence of grade 2-3 late skin toxicity at 5 years was 10·7% (95% CI 8·0-13·4) in the whole-breast irradiation group versus 6·9% (4·8-9·0) in the APBI group (difference -3·8%, 95% CI -7·2 to 0·4; p=0·020). The cumulative risk of grade 2-3 late subcutaneous tissue side-effects at 5 years was 9·7% (95% CI 7·1-12·3) in the whole-breast irradiation group versus 12·0% (9·4-14·7) in the APBI group (difference 2·4%; 95% CI -1·4 to 6·1; p=0·28). The cumulative incidence of grade 2-3 breast pain was 11·9% (95% CI 9·0-14·7) after whole-breast irradiation versus 8·4% (6·1-10·6) after APBI (difference -3·5%; 95% CI -7·1 to 0·1; p=0·074). At 5 years' follow-up, according to the patients' view, 413 (91%) of 454 patients had excellent to good cosmetic results in the whole-breast irradiation group versus 498 (92%) of 541 patients in the APBI group (p=0·62); when judged by the physicians, 408 (90%) of 454 patients and 503 (93%) of 542 patients, respectively, had excellent to good cosmetic results (p=0·12). No treatment-related deaths occurred, but six (15%) of 41 patients (three in each group) died from breast cancer, and 35 (85%) deaths (21 in the whole-breast irradiation group and 14 in the APBI group) were unrelated. INTERPRETATION: 5-year toxicity profiles and cosmetic results were similar in patients treated with breast-conserving surgery followed by either APBI with interstitial brachytherapy or conventional whole-breast irradiation, with significantly fewer grade 2-3 late skin side-effects after APBI with interstitial brachytherapy. These findings provide further clinical evidence for the routine use of interstitial multicatheter brachytherapy-based APBI in the treatment of patients with low-risk breast cancer who opt for breast conservation. FUNDING: German Cancer Aid.

• MeSH
• brachyterapie škodlivé účinky   MeSH
• časové faktory MeSH
• celková dávka radioterapie MeSH
• duktální karcinom prsu patologie   radioterapie   chirurgie   MeSH
• intraduktální neinfiltrující karcinom patologie   radioterapie   chirurgie   MeSH
• kombinovaná terapie MeSH
• kosmetické přípravky * MeSH
• lidé středního věku MeSH
• lidé MeSH
• lobulární karcinom patologie   radioterapie   chirurgie   MeSH
• mastektomie škodlivé účinky   MeSH
• nádory prsu patologie   radioterapie   chirurgie   MeSH
• následné studie MeSH
• prognóza MeSH
• radiodermatitida diagnóza   etiologie   MeSH
• segmentální mastektomie škodlivé účinky   MeSH
• senioři MeSH
• staging nádorů MeSH
• stupeň nádoru MeSH
• tuková nekróza diagnóza   etiologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

INTRODUCTION: Breast-conserving treatment (BCT) consisting of a lumpectomy followed by radiation is considered the standard of care in early-stage breast cancer, and breast reconstruction using fat transfer has become the standard of care in these patients. Immediately following BCT, patients are theoretically the most prone for cancer recurrence caused by the remaining mass of glandular tissue. Therefore, we conducted a prospective study to evaluate the oncological safety of fat grafting in patients after BCT. METHODS: We analyzed patients who underwent breast reconstruction after BCT between April 2011 and February 2014. The control subjects were matched from a prospective database of women treated for breast cancer who did not undergo fat grafting, and each control was matched for the following variables: date of primary cancer surgery, date of fat grafting, histology, estrogen and progesterone receptors (ER+PR), adjuvant hormone therapy, disease-free interval from primary operation (BCT), and disease-free interval from breast reconstruction involving fat grafting. The primary endpoint of this study was tumor recurrence. RESULTS: The study group consisted of 32 patients, while the control group consisted of 45 patients. Breast tumor recurrence was observed in 2 of 32 cases (6.25%) in the reconstruction group, and distant metastases were detected in both cases. In the control group without reconstruction, we found cancer recurrence in 2 of 41 cases (4.88%), and locoregional recurrence was observed in both cases. The difference in cancer recurrence after BCT was insignificant between groups (p = 0.593). CONCLUSION: The recurrence rate in patients reconstructed with fat grafts after BCT was not significantly different from the recurrence rate of control BCT patients.

• MeSH
• dospělí MeSH
• duktální karcinom prsu patologie   chirurgie   MeSH
• incidence MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• lobulární karcinom patologie   chirurgie   MeSH
• lokální recidiva nádoru diagnóza   epidemiologie   MeSH
• mamoplastika * MeSH
• nádory prsu patologie   chirurgie   MeSH
• následné studie MeSH
• prognóza MeSH
• prospektivní studie MeSH
• segmentální mastektomie * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• studie případů a kontrol MeSH
• stupeň nádoru MeSH
• tuková tkáň transplantace   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
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

Úvod: Již delší dobu se diskutuje problematika zařazení magnetické rezonance (MR) do předoperačního stagingu nově diagnostikovaného karcinomu prsu. Cílem takové změny ve vyšetřovacím algoritmu je získání doplňující informace, která může mít za následek změnu rozsahu operačního výkonu oproti původně zamýšlenému na základě konvenčních mamodiagnostických metod. Metoda: V našem souboru figuruje 161 operantek, přičemž u 47 z nich byla indikována v rámci předoperačního stagingu magnetická rezonance prsu. K magnetické rezonanci jsme přistoupili u pacientek s biopticky ověřeným ložiskem lobulárního karcinomu, mladších pacientek s invazivním karcinomem a pacientek s diagnostikovaným DCIS. Dále u pacientek, u nichž byla konvenčními zobrazovacími metodami vyjádřena suspekce na dodatečné ipsilaterální/kontralaterální ložisko či byla přímo potvrzena jeho přítomnost, nebo dalo-li se tak předpokládat na základě imunohistochemické povahy a rozsahu primárního tumoru často ve vztahu k věku, nakonec i u pacientek s bazálním uložením tumorózní léze. Výsledky: U 12 pacientek došlo na základě MR nálezu k upstagingu, ať už ve smyslu rozsahu primárního tumoru, či ve smyslu multifokality, multicentricity či bilaterálního karcinomu. V osmi případech bylo tedy konvertováno v úmyslu na mastektomii a ve čtyřech případech byl proveden extenzivnější resekční výkon. Nelze však opomenout, že v porovnání s definitivní histopatologií preparátu se ukázaly dva MR nálezy jako nepřesné. V našem souboru vedla falešná pozitivita MR k nadbytečnému operačnímu výkonu zatím jen u jedné pacientky. Závěr: Přestože se jedná o soubor pacientek za 3 roky, nejedná se o soubor příliš veliký. I tak vidíme zařazení MR prsu do stávajícího předoperačního vyšetřovacího algoritmu jako velmi přínosné. V naší statistice magnetická rezonance doplnila dosavadní nález, a změnila tak rozsah operačního výkonu celkem u čtvrtiny pacientek takto vyšetřených.

Introduction: The inclusion of an MRI as a part of pre-surgery staging for a newly-discovered breast tumour has been the subject of discussion for some time now. The intent behind incorporating an MRI into the general diagnostic procedure is to gain additional information that could potentially lead to significantly altering the scope of a forthcoming operation. The scope of procedures in the past has been established on the basis of the conventional mammodiagnostic method. Method: Our patient focus group consists of 161 women. Forty-seven of these women were selected to undergo an MRI breast scan as a part of their pre-surgery staging. For those patients with a confirmed deposit of lobular carcinoma, younger patients with invasive carcinoma, and patients diagnosed with DCIS, an MRI scan was an included as a part of the diagnostic procedure. An MRI breast scan was also conducted on women for whom the conventional mammodiagnostic methods either suggested a high probability of additional ipsilateral/contralateral deposits or actually established their presence. Finally, an MRI scan was conducted on patients for whom tumour occurrence had been assumed on the basis of an imunohistochemical characterization and the extent of the initial tumour with regard to the patient’s age, as well as on those patients who suffered from a basal deposit of a cancerous lesion. Results: The inclusion of an MRI breast scan led to an upstaging in twelve patients, either in terms of their primary tumour or in terms of multifocality, multicentricity, or bilateral carcinoma. In eight cases this led to the proposal of a more drastic surgical procedure (mastectomy), and in four cases the scan indicated a need for a more extensive surgical resection. It must be noted that a comparison with decisive results of histopathology showed that two of the MRI scans were imprecise. The apparent inaccuracy of the MRI scan affected only one of the patients, whose surgical procedure consequently extended beyond the necessary scope. Conclusion: Although the focus group contains patients treated within the span of three years, it is still a rather small collection. Nevertheless, the addition of an MRI breast scan to the present pre-surgery diagnostic procedure should be regarded as very beneficial. According to the statistics available at our surgical department, the scope of surgery changed in 25% of cases where the conventional diagnosis method was supplemented with an MRI breast scan.

• Klíčová slova
• upstaging,
• MeSH
• dospělí MeSH
• duktální karcinom prsu diagnóza   chirurgie   patologie   MeSH
• falešně pozitivní reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• lobulární karcinom diagnóza   chirurgie   patologie   MeSH
• magnetická rezonanční tomografie * MeSH
• mucinózní adenokarcinom diagnóza   chirurgie   patologie   MeSH
• nádory prsu * diagnóza   chirurgie   patologie   MeSH
• radikální mastektomie MeSH
• retrospektivní studie MeSH
• senzitivita a specificita MeSH
• staging nádorů * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: Although trastuzumab-containing therapies prolong survival in patients with metastatic breast cancer (MBC), most tumors develop trastuzumab resistance, potentially mediated by aberrant phosphatidylinositide 3-kinase (PI3K)/AKT signaling. Ridaforolimus (a mammalian target of rapamycin [mTOR] inhibitor) may overcome trastuzumab resistance by inhibiting PI3K signaling. METHODS: A single-arm, phase IIb trial was conducted to evaluate the efficacy and safety of ridaforolimus-trastuzumab in human epidermal growth factor receptor 2-positive (HER2(+)) trastuzumab-refractory MBC (NCT00736970). Ridaforolimus was administered orally (40 mg daily) for 5 d/wk plus weekly trastuzumab. The primary end point was objective response (OR). RESULTS: Thirty-four patients were enrolled (91% had received 1 or 2 previous trastuzumab-based therapies, whereas 9% had received 3 previous therapies). The most common reasons for discontinuation were disease progression (62%) and adverse events (AEs; 24%). Three patients died; 1 because of bowel perforation, which was possibly ridaforolimus related. Partial response was observed in 5 patients (15%). Median duration of response was 19.1 weeks (range, 15.9-80.1 weeks). Fourteen patients (41%) achieved stable disease (SD); 7 patients (21%) maintained SD for ≥ 24 weeks. The clinical benefit response (CBR) rate was 34.3%. Median progression-free survival (PFS) and overall survival (OS) were 5.4 months (range, 0-20.3 months; 95% confidence interval [CI], 2.0-7.4) and 17.7 months (range, 0-25.9 months; 95% CI, 8.8-20.8), respectively. PFS rate at 6 months was 37%. The most common treatment-related AEs were stomatitis (59%), diarrhea (27%), and rash (27%). CONCLUSION: Ridaforolimus-trastuzumab was well tolerated and demonstrated antitumor activity in trastuzumab-resistant HER2(+) MBC.

• MeSH
• analýza přežití MeSH
• aplikace orální MeSH
• chemorezistence účinky léků   MeSH
• dospělí MeSH
• duktální karcinom prsu farmakoterapie   mortalita   patologie   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory prsu farmakoterapie   mortalita   patologie   MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   škodlivé účinky   MeSH
• receptor erbB-2 metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sirolimus aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• trastuzumab 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 II MeSH
• multicentrická studie MeSH