共查询到20条相似文献,搜索用时 0 毫秒
1.
J. Thaddeus Beck Gabriel N. Hortobagyi Mario Campone Fabienne Lebrun Ines Deleu Hope S. Rugo Barbara Pistilli Norikazu Masuda Lowell Hart Bohuslav Melichar Shaker Dakhil Matthias Geberth Martina Nunzi Daniel Y. C. Heng Thomas Brechenmacher Mona El-Hashimy Shyanne Douma Francois Ringeisen Martine Piccart 《Breast cancer research and treatment》2014,143(3):459-467
The present exploratory analysis examined the efficacy, safety, and quality-of-life effects of everolimus (EVE) + exemestane (EXE) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting. In BOLERO-2, patients with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2?) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor (NSAI) were randomly assigned (2:1) to receive EVE (10 mg/day) + EXE (25 mg/day) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local assessment. Overall, 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37). Median PFS by local investigator assessment nearly tripled to 11.5 months with EVE + EXE from 4.1 months with PBO + EXE (hazard ratio = 0.39; 95 % CI 0.25–0.62), while maintaining quality of life. This was confirmed by central assessment (15.2 vs 4.2 months; hazard ratio = 0.32; 95 % CI 0.18–0.57). The marked PFS improvement in patients receiving EVE + EXE as first-line therapy for disease recurrence during or after (neo)adjuvant NSAI therapy supports the efficacy of this combination in the first-line setting. Furthermore, the results highlight the potential benefit of early introduction of EVE + EXE in the management of HR+, HER2? advanced breast cancer in postmenopausal patients. 相似文献
2.
Lips EH Mulder L de Ronde JJ Mandjes IA Vincent A Vrancken Peeters MT Nederlof PM Wesseling J Rodenhuis S 《Breast cancer research and treatment》2012,131(3):827-836
A pathological complete remission (pCR) is rarely achieved by neoadjuvant chemotherapy in estrogen receptor-positive (ER+)
HER2-negative (HER2−) tumors. Therefore, its use might be questionable in specific groups of this tumor type. To select which
patients benefit and which could be spared neoadjuvant chemotherapy, we tested standard pathology and molecular markers in
ER+ HER2− breast tumors. Pretreatment biopsies were available from 211 ER+ HER2− tumors, who had been treated with neoadjuvant
chemotherapy (adriamycin/cyclophosphamide). mRNA expression data were available for 132 tumors. We determined progesterone
receptor expression (PR), endocrine sensitivity, HER2 expression, histology, proliferation, and molecular subtypes. We correlated
these data to chemotherapy response using pCR rates and the previously published neoadjuvant response index (NRI). PR-negative
tumors (n = 65, 30.8%) and luminal B type tumors (n = 43, 20.4%) responded significantly better to chemotherapy than other tumors. These associations remained significant in
multivariate analysis. However, even in the subgroup of patients with the lowest response rate, comprising tumors that had
both a positive-PR expression and the luminal A subtype (n = 58, 44%), the majority of the patients had downstaging because of chemotherapy. For histology (lobular vs. ductal), endocrine
sensitivity, and proliferation, no associations with chemotherapy response were observed. Gene expression array analysis resulted
in 28 significant genes (FDR < 0.1). PR expression and luminal B status are associated with a better response to neoadjuvant
chemotherapy. However, both markers had only weak response predictive power, and it was not possible to identify a subgroup
with no or only minimal chemotherapy benefit. Therefore, the decision to refrain from neoadjuvant chemotherapy to ER+ HER2−
breast tumors should not be based on predictive markers, but exclusively on estimates of prognosis. 相似文献
3.
Lu Zhang Qingzhao Yu Xiao-Cheng Wu Mei-Chin Hsieh Michelle Loch Vivien W. Chen Elizabeth Fontham Tekeda Ferguson 《Breast cancer research and treatment》2018,169(1):175-187
Purpose
To investigate the impact of chemotherapy relative dose intensity (RDI) on cause-specific and overall survival for stage I–III breast cancer: estrogen receptor or progesterone receptor positive, human epidermal-growth factor receptor negative (ER+/PR+ and HER2-) vs. triple-negative (TNBC) and to identify the optimal RDI cut-off points in these two patient populations.Methods
Data were collected by the Louisiana Tumor Registry for two CDC-funded projects. Women diagnosed with stage I–III ER+/PR+, HER2- breast cancer, or TNBC in 2011 with complete information on RDI were included. Five RDI cut-off points (95, 90, 85, 80, and 75%) were evaluated on cause-specific and overall survival, adjusting for multiple demographic variables, tumor characteristics, comorbidity, use of granulocyte-growth factor/cytokines, chemotherapy delay, chemotherapy regimens, and use of hormone therapy. Cox proportional hazards models and Kaplan–Meier survival curves were estimated and adjusted by stabilized inverse probability treatment weighting (IPTW) of propensity score.Results
Of 494 ER+/PR+, HER2- patients and 180 TNBC patients, RDI < 85% accounted for 30.4 and 27.8%, respectively. Among ER+/PR+, HER2- patients, 85% was the only cut-off point at which the low RDI was significantly associated with worse overall survival (HR = 1.93; 95% CI 1.09–3.40). Among TNBC patients, 75% was the cut-off point at which the high RDI was associated with better cause-specific (HR = 2.64; 95% CI 1.09, 6.38) and overall survival (HR = 2.39; 95% CI 1.04–5.51).Conclusions
Higher RDI of chemotherapy is associated with better survival for ER+/PR+, HER2- patients and TNBC patients. To optimize survival benefits, RDI should be maintained ≥ 85% in ER+/PR+, HER2- patients, and ≥ 75% in TNBC patients.4.
Kristensen Kristoffer B. Thomsen Ida Marie Nedergaard Berg Tobias Kodahl Annette R. Jensen Anders Bonde 《Breast cancer research and treatment》2021,188(3):799-809
Breast Cancer Research and Treatment - Treatment for estrogen receptor positive (ER+), human epidermal receptor 2 negative (HER2?) metastatic breast cancer (MBC) has improved with the... 相似文献
5.
Joyce O’Shaughnessy Katarina Petrakova Gabe S. Sonke Pierfranco Conte Carlos L. Arteaga David A. Cameron Lowell L. Hart Cristian Villanueva Erik Jakobsen Joseph T. Beck Deborah Lindquist Farida Souami Shoubhik Mondal Caroline Germa Gabriel N. Hortobagyi 《Breast cancer research and treatment》2018,168(1):127-134
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.6.
Masakazu Toi Kenichi Inoue Norikazu Masuda Hiroji Iwata Joohyuk Sohn In Hae Park Seock-Ah Im Shin-Cheh Chen Sotaro Enatsu P. Kellie Turner Valérie A. M. André Molly C. Hardebeck Sachi Sakaguchi Matthew P. Goetz George W. Sledge Jr 《Cancer science》2021,112(6):2381-2392
This post hoc analysis of MONARCH 2 and MONARCH 3 assesses the efficacy, safety, and pharmacokinetics (PK) of abemaciclib in combination with endocrine therapy (ET) in East Asian patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer. MONARCH 2 and MONARCH 3 are global, randomized, double-blind, phase 3 studies of abemaciclib/placebo + fulvestrant and abemaciclib/placebo + nonsteroidal aromatase inhibitor (NSAI, anastrozole or letrozole), respectively. The East Asian population comprised 212 (31.7%) of the 669 intent-to-treat (ITT) population in the MONARCH 2 trial and 144 (29.2%) of the 493 ITT patients in the MONARCH 3 trial. In the East Asian population, median progression-free survival (PFS) was significantly prolonged in the abemaciclib arm compared with placebo in both MONARCH 2 (hazard ratio [HR], 0.520; 95% confidence interval [CI], 0.362 to 0.747; P < .001; median: 21.2 vs 11.6 months) and MONARCH 3 (HR, 0.326; 95% CI, 0.200 to 0.531, P < .001; median: not reached vs 12.82 months). Diarrhea (MONARCH 2: 90%; MONARCH 3: 88%) and neutropenia (MONARCH 2: 68%; MONARCH 3: 58%) were the most frequent adverse events observed in the East Asian populations. Abemaciclib exposures and PK were similar in East Asians and the non-East Asian populations of both trials. Abemaciclib in combination with ET in the East Asian populations of MONARCH 2 and MONARCH 3 provided consistent results with the ITT populations, demonstrating improvements in efficacy with generally tolerable safety profiles for patients with HR+, HER2− advanced breast cancer. 相似文献
7.
Clinical and Translational Oncology - Breast cancer with positive hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) is a special subgroup with different clinical features... 相似文献
8.
9.
10.
11.
R Exner Z Bago-Horvath R Bartsch M Mittlboeck V P Retèl F Fitzal M Rudas C Singer G Pfeiler M Gnant R Jakesz P Dubsky 《British journal of cancer》2014,111(5):837-842
Background:
Validated multigene signatures (MGS) provide additional prognostic information when evaluating clinical features of ER+, HER2− early breast cancer. We have studied the quantitative and qualitative impact of MGS on multidisciplinary team (MDT) recommendations.Methods:
We prospectively recruited 75 ER+, HER2− breast cancer patients. Inclusion was based on biopsy assessment of grade, hormone receptor status, HER2, clinical tumour and nodal status. A fresh tissue sample was sent for MammaPrint (MP), TargetPrint analysis at surgery. Clinical risk was decided by the MDT in the absence of MP results and repeated following the collection of MP results. Decision changes were recorded and a health technology assessment was undertaken to compare cost effectiveness.Results:
The majority of patients were assigned low to intermediate clinical risk by the MDT. According to MP, 76% were low risk. A very high correlation between local IHC and the TargetPrint assessment was shown. In over a third of patients, discordance between clinical and molecular risk was observed. Decision changes were recorded in half of these cases (18.6%) and resulted in two out of three patients not requiring chemotherapy. The use of MP was also found to be more cost effective.Conclusions:
The multigene signature MP revealed clinical and molecular risk discordance in a third of patients. The impact of this on MDT recommendations was most profound in cases where few clinical risk factors were observed and enabled some women to forgo chemotherapy. The use of MGS is unlikely to have an impact in either clinically low-risk women or in patients with more than one relative indication for chemotherapy. 相似文献12.
M. E. Roseland K. Schwartz J. J. Ruterbusch L. Lamerato R. Krajenta J. Booza Michael S. Simon 《Breast cancer research and treatment》2017,165(1):163-168
Background
African American (AA) women with breast cancer have persistently higher mortality compared to whites. We evaluated racial disparities in mortality among women with estrogen receptor (ER)/progesterone receptor (PR)-negative breast cancer.Methods
The study population included 542 women (45% AA) diagnosed with ER/PR-negative Stage I through III breast cancer treated at the Henry Ford Health System (HFHS) between 1996 and 2005. Linked datasets from HFHS, Metropolitan Detroit Cancer Surveillance System, and the U.S. Census Bureau were used to obtain demographic, socioeconomic, and clinical information. Economic deprivation was categorized using a previously validated deprivation index, which included 5 categories based on the quintile of census tract socioeconomic deprivation. Cox proportional hazards models were used to assess the relationship between race and mortality.Results
AA women were more likely to have larger tumors, have higher Charlson Comorbidity Indices (CCI), and to reside in economically deprived areas. In an unadjusted analysis, AA women demonstrated a significantly higher risk of death compared to whites [hazard ratio (HR) 1.47, 95% confidence interval (CI) 1.09–2.00]. Following adjustment for clinical factors (age, stage, CCI) and treatment (radiation and chemotherapy), AA race continued to have a significant impact on mortality (HR 1.51, CI 1.10–2.08 and HR 1.63, CI 1.20–2.21). Only after adjusting for deprivation was race no longer significant (HR 1.26, CI 0.84–1.87).Conclusions
Social determinants of health play a large role in explaining racial disparities in breast cancer outcomes, especially among women with aggressive subtypes.13.
Mehra Golshan Constance T. Cirrincione William M. Sikov Lisa A. Carey Donald A. Berry Beth Overmoyer Nora L. Henry George Somlo Elisa Port Harold J. Burstein Clifford Hudis Eric Winer David W. Ollila for the Alliance for Clinical Trials in Oncology 《Breast cancer research and treatment》2016,158(2):297-305
14.
Rinat Yerushalmi Hagen Kennecke Ryan Woods Ivo A. Olivotto Caroline Speers Karen A. Gelmon 《Breast cancer research and treatment》2009,117(2):365-370
Purpose we evaluated whether patients with multifocal/multicentric (M/M) breast cancer have different outcomes compared to unifocal
(U) disease in terms of survival and the development of contralateral breast cancer (CBC) disease. Methods women diagnosed with stage I–III breast cancer were classified as having U or M/M disease. Prognostic factors were prospectively
collected and obtained from the breast cancer outcome unit database. Univariate and multivariable analyses for the incidence
of CBC were performed as well as Kaplan–Meier plots. Results 25,320 women met inclusion criteria. The 5-year cumulative incidence of CBC in the U versus M/M group was 2.3% (95% CI 2.1,
2.5) versus 2.4% (95% CI 1.6, 3.4) (P = 0.349). Breast cancer specific survival (BCSS) rate revealed a slightly worse outcome with M/M disease, RR = 1.174 (95%
CI 1,004, 1.372). Conclusions M/M breast cancer did not increase the risk of metachronous CBC, but was associated with inferior BCSS. 相似文献
15.
Spears M Taylor KJ Munro AF Cunningham CA Mallon EA Twelves CJ Cameron DA Thomas J Bartlett JM 《Breast cancer research and treatment》2012,132(2):463-470
HER2 overexpression/amplification is linked with poor prognosis in early breast cancer. Co-expression of HER2 and HER3 is
associated with endocrine and chemotherapy resistance, driven not simply by expression but by signalling via HER2:HER3 or
HER2:HER2 dimers. Proximity ligation assays (PLAs) detect protein–protein complexes at a single-molecule level and allow study
of signalling pathways in situ. A cohort of 100 tumours was analyzed by PLA, IHC and FISH. HER complexes were analyzed by
PLA in a further 321 tumours from the BR9601 trial comparing cyclophosphamide, methotrexate and fluorouracil (CMF) with epirubicin
followed by CMF (epi-CMF). The relationships between HER dimer expression and RFS and OS were investigated, and multivariate
regression analysis identified factors influencing patient prognosis. PLA successfully and reproducibly detected HER2:HER2
and HER2:HER3 protein complexes in vivo. A significant association (P < 0.00001) was identified between HER2 homodimerization and HER2 gene amplification. Following a minimum p value approach
high levels of HER2:HER2 dimers were significantly associated with reduced relapse-free (RFS; hazard ratio = 1.72, 95% confidence
interval 1.15–2.56, P = 0.008) and overall survival (OS HR = 1.69 95% CI = 1.09–2.62, P = 0.019). Similarly, high levels of HER2:HER3 dimers were associated with reduced RFS (HR = 2.18, 95% CI = 1.46–3.26, P = 0.00016) and OS (HR = 2.21, 95% CI = 1.41–3.47, P = 0.001). This study demonstrates that in situ detection of HER2 and HER2:3 protein:protein complexes can be performed robustly
and reproducibly in clinical specimens, provides novel prognostic information and opens a significant novel opportunity to
probe the clinical impact of cellular signalling processes. 相似文献
16.
Dowsett M Cooke T Ellis I Gullick WJ Gusterson B Mallon E Walker R 《European journal of cancer (Oxford, England : 1990)》2000,36(2):170-176
Human epidermal growth factor receptor 2 (HER2) is overexpressed, usually as a result of HER2 proto-oncogene amplification, in 20-30% of breast cancers. A HER2-positive status is generally associated with more aggressive disease and a worse prognosis. Furthermore, a positive HER2 status may predict the likelihood of resistance to some conventional therapies, as well as probably being predictive of sensitivity to anthracycline dose intensification. In addition to this prognostic/predictive value, HER2 is a target for specific therapy, with anti-HER2 monoclonal antibody therapy available in the USA. This article reviews the different assays used to determine HER2 status, discussing their relative advantages/disadvantages and the need for their standardisation before integration alongside other pathological indices into the clinical management of breast cancer. 相似文献
17.
Diep Ho Jessica Huang Judith-Anne W. Chapman Kim Leitzel Suhail M. Ali Lois Shepherd Wendy R. Parulekar Catherine E. Ellis Rocco J. Crescnzo Liting Zhu Shakeel Virk Dora Nomikos Samuel Aparicio Karen A. Gelmon Walter P. Carney Allan Lipton 《Breast cancer research and treatment》2017,162(3):571-580
Purpose
To examine the association of plasma carotenoids, micronutrients in fruits, and vegetables, with risk of premalignant breast disease (PBD) in younger women.Methods
Blood samples were collected at the Siteman Cancer Center between 2008 and 2012 from 3537 women aged 50 or younger with no history of cancer or PBD. The analysis included 147 participants diagnosed with benign breast disease or breast carcinoma in situ during a 27-month follow-up and 293 controls. Cases and controls were matched on age, race/ethnicity, and date of and fasting status at blood draw. Plasma carotenoids were quantified. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and linear regression to assess racial differences in plasma carotenoids.Results
The risk reduction between the highest and lowest tertiles varied by carotenoid, with β-cryptoxanthin having the greatest reduction (OR 0.62; 95% CI, 0.62–1.09; P trend = 0.056) and total carotenoids the least (OR 0.83; 95% CI, 0.48–1.44; P trend = 0.12). We observed an inverse association between plasma carotenoids and risk of PBD in obese women (BMI ≥ 30 kg/m2; 61 cases and 115 controls) but not lean women (BMI < 25 kg/m2; 54 cases and 79 controls), although the interaction was not statistically significant. Compared to white women, black women had lower levels of α and β-carotene and higher levels of β-cryptoxanthin and lutein/zeaxanthin.Conclusions
We observed suggestive inverse associations between plasma carotenoids and risk of PBD in younger women, consistent with inverse associations reported for invasive breast cancer. Carotenoids may play a role early in breast cancer development.18.
Giulia Viale Stefania Morganti Emanuela Ferraro Paola Zagami Antonio Marra Giuseppe Curigliano 《Expert review of anticancer therapy》2013,13(9):811-822
ABSTRACTIntroduction: Despite dramatic improvements in survival achieved with currently available anti-HER2 agents, HER2-positive metastatic breast cancer remains an almost invariably deadly disease, with primary or acquired resistance to HER2-directed agents developing during treatment. Many efforts are focused on identifying new agents that may more effectively inhibit HER2 signaling and on possible combination strategies.Areas covered: This review summarizes the landscape of drugs under development for HER2-positive metastatic breast cancer, as antibody-drug conjugates, monoclonal anti-HER2 antibodies, bispecific antibodies, or novel tyrosine kinase inhibitors. Moreover, available data for possible combination of anti-HER2 drugs and different agents, as immunotherapy, PI3K/mTOR inhibitors, CDK4/6 inhibitors currently under evaluation are reviewed. These strategies may overcome mechanisms of resistance and further improve patient outcomes.Expert opinion: Identification of valuable predictive biomarkers is needed to better inform choice of treatment sequence for the individual patient and limit the financial toxicity of these agents. 相似文献
19.
Journal of Neuro-Oncology - 相似文献