Identification of a basal-like subtype and comparative effect of epirubicin-based chemotherapy and sequential epirubicin followed by docetaxel chemotherapy in the PACS 01 breast cancer trial: 33 markers studied on tissue-microarrays (TMA)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 509-509 ◽  
Author(s):  
J. Jacquemier ◽  
F. Penault-Llorca ◽  
H. Mnif ◽  
E. Charafe-Jauffret ◽  
S. Marque ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tissue Microarrays ◽  
Therapeutic Benefit ◽  
Normal Breast ◽  
Phase Iii ◽  
Rank Test ◽  
Cancer Trial ◽  
Er Positive ◽  
The Impact ◽  
Docetaxel Chemotherapy

509 Background: Immunohistochemical profiling studies with TMA classified breast cancer by luminal, normal breast like, HER-2 overexpressing, and basal-like subtypes. The aim of this study was to evaluate the impact of these subclasses in terms of therapeutic benefit for patients (pts) with node positive operable breast cancer included in the phase III trial PACS01. Methods: Among the 1999 pts randomized, 1100 paraffin blocs were collected for TMA. Pts were treated with either arm A: 6 cycles of FEC100 (546 pts) or arm B: docetaxel 100 mg/m2 replaced FEC100 for the last 3 cycles (554 pts). The median follow up was 5 years. The 33 analysed markers explored different pathways: cellular differentiation (CK5/6,8/18,14, P-Cadherin, E-cadherin, α-catenin, β-catenin, AF6, MUC1, Cav1, moesin, Cd10, CD44), proliferation/apoptosis (AuroraA, Tacc2/3, Ki67, CyclinD1, Bcl2, p21, p27), ER related (ER, PR, Gata3), and oncogene/ antioncogene (P53, HER2, EGFR1, Pten, Cmet, Fhit, FGFR, Angiogenin, topoisomeraseIIα). All antibodies were evaluated in quick score. Results: In terms of metastases free survival (MFS) 16 markers harboured a statistical significant value under 20%. The hierarchical clustering for 80% of complete data, identify a cluster of pts (n=531) characterized by the positive expression of EGFR1, Moesin, Pcadherin, and p53, considered as basal-like subtype (BLST). This cluster presented a pejorative predictive value both in Log-rank test (LR) (p=0.002) and in Cox multivariate analysis (HR=0.65; p=0.009), confirmed in overall survival (OS) (LR p<0.0001; cox HR=0.46, p<0.001). BLST pts had a significantly better MFS (LR p=0.05) in the arm B, confirmed in OS (LR p=0.005), as for a more theoretical basal signature and ER negativity (LR MFS p=0.0033, OS p=0.0052; cox MFS HR=0.71 p=0.04, OS HR=0.51 p=0.003). For a second cluster considered as luminal subtype (ER positive and BLST parameters negatives) no difference was observed whatever the arm. Conclusions: The basal-like profile identified in this study is significantly associated to a worst prognostic, but also to a better response to sequential FEC/docetaxel chemotherapy. [Table: see text]

Sequence of anthracyclines and taxanes in the neoadjuvant chemotherapy of HER2-negative breast cancer: Experience of a Brazilian oncological center.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12105-e12105
Author(s):  
Daniel D’Almeida Preto ◽  
André Octavio Nicolau Sanches ◽  
Alison Wagner Azevedo Barroso ◽  
Alessandra Caroline Moretto Carbinatto ◽  
Ana Lima Veneziani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Cancer Center ◽  
Survival Times ◽  
Number Of Patients ◽  
The Impact

e12105 Background: The best sequence of anthracyclines and taxanes in the neoadjuvant chemotherapy of HER2-negative breast cancer is still unknown. The aims of this study were to assess the impact of the sequence order in the pathological complete response (pCR) rate, and in the disease free survival (DFS) and overall survival (OS). Methods: We retrospectively reviewed 235 HER2-negative breast cancer women treated with neoadjuvant chemotherapy from 2003 to 2011 at our cancer center. The patients were pooled in two groups: anthracycline-based followed by taxanes (AC-T) and the reverse sequence (T-AC). The chi-square test was performed to verify the homogeneity between the groups and to compare pCR rate among the treatment groups. Cumulative survival probabilities were calculated using the Kaplan-Meier method. Differences between survivals were tested using the log-rank test. Results: The AC-T (n = 161) and T-AC (n = 74) groups were balanced for age, staging, receptor profile and histologic grade. The follow-up was at least five years for each patient. The median age was 50.1 years. Most patients (97%) had stage III tumors and 72 (30%) had triple negative disease. pCR rate was higher in triple negative compared with luminal cases (16.3 vs. 7.3%; p = 0.049). Treatment sequence did not influence the occurrence of pCR (10.5 vs. 8.5%; p = 0.8) or median survival times (DFS: 87.9 vs. 64.1, p = 0.85; OS: 91.1 vs. 71.6 months, p = 0.15), in the AC-T and T-AC groups, respectively. Conclusions: The sequence of neoadjuvant taxane-anthracycline-based chemotherapy regimen in daily practice did not show difference in the evaluated clinical outcomes. The retrospective design and the low number of patients may limit the power of the study to detect statistically significant differences. Phase III trials should be stimulated in this context. [Table: see text]

Differences in psychosocial factors among diverse women enrolled in a phase III cooperative group metastatic breast cancer trial (CALGB 40502/Alliance).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9581-9581
Author(s):  
Blase N. Polite ◽  
Jacob B Allred ◽  
Hope S. Rugo ◽  
Toni Marie Cipriano ◽  
Constance Cirrincione ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Social Support ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Cooperative Group ◽  
Breast Cancer Patients ◽  
Cancer Trial ◽  
Race Ethnicity ◽  
The Impact

9581 Background: Previous metastatic breast cancer trials have shown lower overall survival among African American (AA) women. Studies have also shown links between higher comorbidities and lower levels of social support and survival. Whether these factors differ by race and ethnicity is not known. Methods: Breast cancer patients enrolling in a phase III cooperative group metastatic breast cancer trial completed a self-administered survey measuring psychosocial and socio-demographic factors and comorbidities. Results were analyzed by self-identified race/ethnicity and evaluated by other measured variables. Results: 703 out of 799 patients completed the survey (88%). Questions were answered by greater than 95% of participants. The table shows differences broken down by Race/Ethnicity. AA and Hispanic (H) patients were more likely to have trouble paying for medications and have incomes less than 15K per year. AA were less likely to be married, and had lower levels of social support. Differences in income did not mediate these social support differences. Marital status did not mediate lower social support for AA (p=0.79) but did so for whites (p<0.001) Conclusions: Compliance with the questionnaire was quite high. Differences in social support by race were apparent and were mediated by different factors according to race. Future efforts will analyze the impact of these factors on survival and as mediators for potential racial and ethnic differences in survival. [Table: see text]

scholarly journals Ovarian cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sarah M. Bernhardt ◽  
Pallave Dasari ◽  
Danielle J. Glynn ◽  
Lucy Woolford ◽  
Lachlan M. Moldenhauer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Menstrual Cycle ◽  
Recurrence Score ◽  
Gene Signature ◽  
Ovarian Cycle ◽  
Oncotype Dx ◽  
Mammary Tumours ◽  
Er Positive ◽  
The Impact

Abstract Background The Oncotype DX 21-gene Recurrence Score is predictive of adjuvant chemotherapy benefit for women with early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. In premenopausal women, fluctuations in estrogen and progesterone during the menstrual cycle impact gene expression in hormone-responsive cancers. However, the extent to which menstrual cycling affects the Oncotype DX 21-gene signature remains unclear. Here, we investigate the impact of ovarian cycle stage on the 21-gene signature using a naturally cycling mouse model of breast cancer. Methods ER-positive mammary tumours were dissected from naturally cycling Mmtv-Pymt mice at either the estrus or diestrus phase of the ovarian cycle. The Oncotype DX 21-gene signature was assessed through quantitative real time-PCR, and a 21-gene experimental recurrence score analogous to the Oncotype DX Recurrence Score was calculated. Results Tumours collected at diestrus exhibited significant differences in expression of 6 Oncotype DX signature genes (Ki67, Ccnb1, Esr1, Erbb2, Grb7, Bag1; p ≤ 0.05) and a significant increase in 21-gene recurrence score (21.8 ± 2.4; mean ± SEM) compared to tumours dissected at estrus (15.5 ± 1.9; p = 0.03). Clustering analysis revealed a subgroup of tumours collected at diestrus characterised by increased expression of proliferation- (p < 0.001) and invasion-group (p = 0.01) genes, and increased 21-gene recurrence score (p = 0.01). No correlation between ER, PR, HER2, and KI67 protein abundance measured by Western blot and abundance of mRNA for the corresponding gene was observed, suggesting that gene expression is more susceptible to hormone-induced fluctuation compared to protein expression. Conclusions Ovarian cycle stage at the time of tissue collection critically affects the 21-gene signature in Mmtv-Pymt murine mammary tumours. Further studies are required to determine whether Oncotype DX Recurrence Scores in women are similarly affected by menstrual cycle stage.

scholarly journals Surgery for primary tumor benefits survival for breast cancer patients with bone metastases: a large cohort retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhangheng Huang ◽  
Xin Zhou ◽  
Yuexin Tong ◽  
Lujian Zhu ◽  
Ruhan Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Predictive Accuracy ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Risk Of Death ◽  
The Impact

Abstract Background The role of surgery for the primary tumor in breast cancer patients with bone metastases (BM) remains unclear. The purpose of this study was to determine the impact of surgery for the primary tumor in breast cancer patients with BM and to develop prognostic nomograms to predict the overall survival (OS) of breast cancer patients with BM. Methods A total of 3956 breast cancer patients with BM from the Surveillance, Epidemiology, and End Results database between 2010 and 2016 were included. Propensity score matching (PSM) was used to eliminate the bias between the surgery and non-surgery groups. The Kaplan-Meier analysis and the log-rank test were performed to compare the OS between two groups. Cox proportional risk regression models were used to identify independent prognostic factors. Two nomograms were constructed for predicting the OS of patients in the surgery and non-surgery groups, respectively. In addition, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the performance of nomograms. Result The survival analysis showed that the surgery of the primary tumor significantly improved the OS for breast cancer patients with BM. Based on independent prognostic factors, separate nomograms were constructed for the surgery and non-surgery groups. The calibration and ROC curves of these nomograms indicated that both two models have high predictive accuracy, with the area under the curve values ≥0.700 on both the training and validation cohorts. Moreover, DCA showed that nomograms have strong clinical utility. Based on the results of the X-tile analysis, all patients were classified in the low-risk-of-death subgroup had a better prognosis. Conclusion The surgery of the primary tumor may provide survival benefits for breast cancer patients with BM. Furthermore, these prognostic nomograms we constructed may be used as a tool to accurately assess the long-term prognosis of patients and help clinicians to develop individualized treatment strategies.

Plasma ESR1 Mutations and the Treatment of Estrogen Receptor–Positive Advanced Breast Cancer

2016 ◽  
Vol 34 (25) ◽  
pp. 2961-2968 ◽  
Author(s):  
Charlotte Fribbens ◽  
Ben O’Leary ◽  
Lucy Kilburn ◽  
Sarah Hrebien ◽  
Isaac Garcia-Murillas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Phase Iii ◽  
Wild Type ◽  
Estrogen Receptor Positive ◽  
Esr1 Mutations ◽  
The Impact

Purpose ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer. Materials and Methods In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. Results In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). Conclusion ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.

Phase I/II trial of tamoxifen with or without fenretinide, an analog of vitamin A, in women with metastatic breast cancer.

1993 ◽  
Vol 11 (3) ◽  
pp. 474-477 ◽  
Author(s):  
M A Cobleigh ◽  
K Dowlatshahi ◽  
T A Deutsch ◽  
R G Mehta ◽  
R C Moon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Vitamin A ◽  
Phase I ◽  
Mammary Cancer ◽  
Metastatic Breast ◽  
Serum Levels ◽  
Phase Iii ◽  
Antitumor Effects ◽  
Er Positive

PURPOSE Considerable attention has been focused on the chemopreventive properties of fenretinide against carcinogen-induced rodent mammary cancer. Less is known about its direct antitumor effects. The combination of tamoxifen and fenretinide is more effective than tamoxifen or fenretinide alone in prevention of rat mammary cancer. However, the combined toxicity of tamoxifen plus fenretinide in humans is unknown. Therefore, we performed a phase I/II trial in women with estrogen receptor (ER)-positive or progesterone receptor (PR)-positive, previously untreated metastatic breast cancer. PATIENTS AND METHODS Groups of three patients received tamoxifen 20 mg/d, or tamoxifen plus fenretinide 100, 200, 300, or 400 mg/d. Patients who received fenretinide enjoyed a 3-day "drug holiday" every 4 weeks. Serum levels of fenretinide and its major metabolites were monitored. Patients were monitored for known toxicities of tamoxifen and vitamin A analogs, as well as for response. RESULTS There were no significant adverse effects on renal, hepatic, hematologic, or lipid values. Nyctalopia, photophobia, cheilitis, and pruritus were not observed. Improvement or stabilization of disease occurred in 12 of 15 patients. CONCLUSION We conclude that tamoxifen administered with fenretinide is nontoxic. Phase III trials of tamoxifen versus tamoxifen plus fenretinide are warranted.

scholarly journals Impact of Genetic Ancestry on Outcomes in ECOG-ACRIN-5103

2017 ◽  
pp. 1-9 ◽  
Author(s):  
Bryan P. Schneider ◽  
Fei Shen ◽  
Guanglong Jiang ◽  
Anne O’Neill ◽  
Milan Radovich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Congestive Heart Failure ◽  
The United States ◽  
Genetic Ancestry ◽  
Phase Iii ◽  
European Ancestry ◽  
Induced Hypertension ◽  
The Impact ◽  
Dose Reductions

Purpose Racial disparity in breast cancer outcomes exists between African American and white women in the United States. We have evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for patients with breast cancer in the context of a randomized, phase III adjuvant trial. Methods This study compared outcomes between 386 patients of African ancestry (AA) and 2,473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial, ECOG-ACRIN-5103. The primary efficacy end point, invasive disease–free survival (DFS), and clinically significant toxicities were compared, including anthracycline-induced congestive heart failure, taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension. Results Overall, AAs had significantly inferior DFS ( P = .002; hazard ratio, 1.5) compared with EAs. This was significant in the estrogen receptor–positive subgroup ( P = .03), with a similar, nonsignificant trend for those who had triple-negative breast cancer ( P = .12). AAs also had significantly more grades 3 to 4 TIPN (odds ratio [OR], 2.9; P = 2.4 × 10−11) and grades 3 to 4 bevacizumab-induced hypertension (OR, 1.6; P = .02), with a trend for more congestive heart failure (OR, 1.8; P = .08). AAs had significantly more dose reductions in paclitaxel ( P = 6.6 × 10−6). In AAs, dose reductions in paclitaxel had a significant negative impact on DFS ( P = .03), whereas in EAs, dose reductions did not have an impact on outcome ( P = .35). Conclusion AAs had inferior DFS, with more clinically important toxicities, in ECOG-ACRIN-5103. The altered risk-to-benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions in paclitaxel, especially as the result of TIPN, are warranted for this population.

Active c-Src has prognostic and therapeutic value in ER-negative breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10063-10063
Author(s):  
A. Arnaout ◽  
L. Yang ◽  
C. Holloway ◽  
N. Steven ◽  
P. Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Significance ◽  
Immunohistochemical Analysis ◽  
Tissue Microarrays ◽  
Distant Recurrence ◽  
Breast Cancers ◽  
Nonreceptor Tyrosine Kinase ◽  
Human Breast Carcinomas ◽  
Er Positive ◽  
Er Status

10063 Background: Approximately 33% of newly diagnosed breast cancers lack ER and these tend to have a worse prognosis as compared to ER-positive breast cancers. Therapeutic options are limited as they are not responsive to antihormonal therapy and often develop resistance to chemotherapies. We have recently shown that activation of the nonreceptor tyrosine kinase protein c-Src leads to the accelerated ER degradation in ER-negative breast cancers. This study performs an immunohistochemical analysis of activated c-Src in a large cohort of primary human breast carcinomas to a) assess its prognostic significance and b) correlate its relationship to the ER status of breast cancers. Methods: A total of 916 patients with breast cancer diagnosed between 1987 and 1997 had clinicopathological data and paraffin-embedded tumor tissues for the study. Tissue microarrays were constructed. A four point scoring system based on immunostaining intensity was used to grade the levels of active phosphorylated c-Src. Grading was done by one pathologist. Statistical analysis was used to assess the prognostic significance of activated c-Src and its relationship to other prognostic variables. Results: Median follow-up was 7.31 years. Active c-Src grade was inversely correlated with ER status (p=0.004) and predicted for treatment with chemotherapy (p=0.002) and lack of treatment with Tamoxifen (p=0.007). Patients with greater levels of c-Src tended to be younger (p=0.004) and had higher Bloom Richardson scores for their tumors (p=0.004). Higher levels of c-Src also predicted for for shorter timing to distant recurrence (p=0.01) and shorter timing to death (p=0.04). There was a trend towards a shorter timing to regional recurrence with higher levels of c-Src but the relationship was not statistically significant (p=0.08). Conclusion: This study supports the hypothesis that the presence of active, phosphorylated c-Src contributes to the development of ER-negative status in breast cancers. The presence of c-Src also is associated with other poor prognostic factors and contributes to a worse prognostic outcome. This study suggests that c-Src inhibitors may be a novel therapeutic strategy for the treatment of ER-negative breast cancers. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document