scholarly journals Androgen receptor signaling pathways as a target for breast cancer treatment

2016 ◽  
Vol 23 (10) ◽  
pp. R485-R498 ◽  
Author(s):  
Elisabetta Pietri ◽  
Vincenza Conteduca ◽  
Daniele Andreis ◽  
Ilaria Massa ◽  
Elisabetta Melegari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Signaling Pathways ◽  
Triple Negative ◽  
Pubertal Development ◽  
Her2 Positive ◽  
Age Related ◽  
Clinical Scenarios ◽  
Er Positive ◽  
Positive Breast Cancer

The androgen receptor (AR) is a ligand-dependent transcription factor, and its effects on breast range from physiological pubertal development and age-related modifications to cancer onset and proliferation. The prevalence of AR in early breast cancer is around 60%, and AR is more frequently expressed in ER-positive than in ER-negative tumors. We offer an overview of AR signaling pathways in different breast cancer subtypes, providing evidence that its oncogenic role is likely to be different in distinct biological and clinical scenarios. In particular, in ER-positive breast cancer, AR signaling often antagonizes the growth stimulatory effect of ER signaling; in triple-negative breast cancer (TNBC), AR seems to drive tumor progression (at least in luminal AR subtype of TNBC with a gene expression profile mimicking luminal subtypes despite being negative to ER and enriched in AR expression); in HER2-positive breast cancer, in the absence of ER expression, AR signaling has a proliferative role. These data represent the rationale for AR-targeting treatment as a potentially new target therapy in breast cancer subset using androgen agonists in some AR-positive/ER-positive tumors, AR antagonists in triple-negative/AR-positive tumors and in combination with anti-HER2 agents or with other signaling pathways inhibitors (including PI3K/MYC/ERK) in HER2-positive/AR-positive tumors. Only the ongoing and future prospective clinical trials will allow us to establish which agents are the best option in every specific condition, keeping in mind that there is evidence of opposite androgens and AR agonist/antagonist drug effects on cell proliferation particularly in AR-positive/ER-positive tumors.

FDG PET/CT during neoadjuvant chemotherapy may predict response in ER-positive/HER2-negative and triple negative, but not in HER2-positive breast cancer

The Breast ◽  
2013 ◽  
Vol 22 (5) ◽  
pp. 691-697 ◽  
Author(s):  
Bas B. Koolen ◽  
Kenneth E. Pengel ◽  
Jelle Wesseling ◽  
Wouter V. Vogel ◽  
Marie-Jeanne T.F.D. Vrancken Peeters ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Fdg Pet ◽  
Triple Negative ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Pet Ct ◽  
Er Positive ◽  
Fdg Pet Ct ◽  
Positive Breast Cancer

Risk factors associated with mortality among women with breast cancer in Haiti.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13069-e13069
Author(s):  
Joseph Bernard ◽  
Garvey Rama Pascal ◽  
Sarah Cassandra Raymond ◽  
Vincent DeGennaro
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
Triple Negative ◽  
Stage Iii ◽  
Her2 Positive ◽  
Haitian Women ◽  
Factors Associated ◽  
Her2 Positive Breast Cancer ◽  
Er Positive ◽  
Positive Breast Cancer

e13069 Background: According to recent estimations of GLOBOCAN 2012, breast cancer is the 2ndmost common cancer among Haitian women. This study aims to describe the epidemiology of breast cancer at a Haitian hospital and to determine the factors associated with mortality. Methods: A retrospective chart review was conducted on women treated for breast cancer at the Innovating Health International Cancer Center, in Port-au-Prince, Haiti. All charts with complete information from 2014 and 2015 were included. Charts were reviewed to collect key variables related to breast cancer. Odds ratios were calculated and Mantel-Haenszel Chi-square test was used to identify the factors associated with mortality. Results: Among the 289 charts reviewed, 275 were selected for this study. The mean age is 51.82 years-old [20 - 100]. 81.1% of the patients had stage III or IV breast cancer at their first consultation. 92% of the women were diagnosed with invasive ductal carcinoma. Of the 165 cases tested for hormone receptor status, 54.5% were ER-positive, 31.5% were triple negative and 12.1% were HER2-enriched. The mortality rate is 24.4%. The odds of dying from breast cancer was significantly higher among women who had their menarche before 15 years old [Odds Ratio (OR) = 4.2; P = 0.02], stage III or IV breast cancer (OR = 3.7; P = 0.01), triple-negative or HER2-positive breast cancer (OR = 2.5; P = 0.01). Mortality was significantly lower among women who benefited from hormone therapy (OR = 0.22; P < 0.01). Conclusions: Breast cancer is often diagnosed at late stages in Haiti, which increases mortality. Women with ER-positive breast cancer survive significantly more than those with HER2-positive or triple-negative breast cancer, mainly due to the availability of hormone therapy and the absence of trastuzumab. A national awareness and screening program has to be implemented to educate Haitian women on breast cancer and increase early diagnosis. As an essential medicine in oncology according to the World Health Organization (WHO), biosimilar trastuzumab needs to be available to increase the survival of patients with HER2-positive breast cancer.

scholarly journals Breast Cancer Subtypes and Response to Docetaxel in Node-Positive Breast Cancer: Use of an Immunohistochemical Definition in the BCIRG 001 Trial

2009 ◽  
Vol 27 (8) ◽  
pp. 1168-1176 ◽  
Author(s):  
Judith Hugh ◽  
John Hanson ◽  
Maggie Chon U. Cheang ◽  
Torsten O. Nielsen ◽  
Charles M. Perou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Luminal A ◽  
Her2 Positive ◽  
Luminal B ◽  
Node Positive ◽  
Er Positive ◽  
Positive Breast Cancer

PurposeTo investigate the prognostic and predictive significance of subtyping node-positive early breast cancer by immunohistochemistry in a clinical trial of a docetaxel-containing regimen.MethodsPathologic data from a central laboratory were available for 1,350 patients (91%) from the BCIRG 001 trial of docetaxel, doxorubicin, and cyclophosphamide (TAC) versus fluorouracil, doxorubicin, and cyclophosphamide (FAC) for operable node-positive breast cancer. Patients were classified by tumor characteristics as (1) triple negative (estrogen receptor [ER]–negative, progesterone receptor [PR]–negative, HER2/neu [HER2]–negative), (2) HER2 (HER2-positive, ER-negative, PR-negative), (3) luminal B (ER-positive and/or PR-positive and either HER2-positive and/or Ki67high), and (4) luminal A (ER-positive and/or PR-positive and not HER2-positive or Ki67high), and assessed for prognostic significance and response to adjuvant chemotherapy.ResultsPatients were subdivided into triple negative (14.5%), HER2 (8.5%), luminal B (61.1%), and luminal A (15.9%). Three-year disease-free survival (DFS) rates (P values with luminal B as referent) were 67% (P < .0001), 68% (P = .0008), 82% (referent luminal B), and 91% (P = .0027), respectively, with hazard ratios of 2.22, 2.12, and 0.46. Improved 3-year DFS with TAC was found in the luminal B group (P = .025) and a combined ER-positive/HER2-negative group treated with tamoxifen (P = .041), with a marginal trend in the triple negatives (P = .051) and HER2 (P = .068) subtypes. No DFS advantage was seen in the luminal A population.ConclusionA simple immunopanel can divide breast cancers into biologic subtypes with strong prognostic effects. TAC significantly complements endocrine therapy in patients with luminal B subtype and, in the absence of targeted therapy, is effective in the triple-negative population.

scholarly journals SABCS 2020: update on triple-negative and metastatic HER2-positive breast cancer

2021 ◽  
Author(s):  
Rupert Bartsch
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Pretreated Patients ◽  
First Line Treatment ◽  
Positive Breast Cancer

SummaryOne year into the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic, the 2020 San Antonio Breast Cancer Symposium (SABCS) was another large congress held in a virtual format. Despite these circumstances, clinically relevant data were presented, and this short review focuses on developments in the fields of triple-negative breast cancer (TNBC) and metastatic HER2-positive breast cancer. A quality-of-life (QoL) analysis from IMPassion031 showed that adding atezolizumab to neoadjuvant chemotherapy was not associated with a detrimental effect on QoL, while the burden of treatment-induced side effects increased with each cycle of neoadjuvant therapy in both treatment arms. KEYNOTE-355 evaluated the addition of pembrolizumab to chemotherapy as first-line treatment in metastatic TNBC (mTNBC); a significant improvement of progression-free survival (PFS) was reported in the pembrolizumab arm. At the 2020 SABCS, results with respect to different chemotherapy backbones were reported and the benefit of pembrolizumab was maintained irrespective of the type of taxane. Disappointingly, the phase III IPATunity130 study could not confirm a PFS improvement with the AKT inhibitor ipatasertib when added to paclitaxel as first-line treatment in mTNBC. A biomarker analysis from the phase III ASCENT study showed that the antibody–drug conjugate sacituzumab govitecan was superior to chemotherapy by investigator’s choice independent of Trop‑2 expression and BRCA mutation status. In HER2-positive breast cancer, the PRECIOUS trial suggested a small albeit significant benefit with reinduction of pertuzumab in later treatment lines in patients progressing on prior dual HER2-blockade in the first- or second-line setting. The HER2-specific tyrosine kinase inhibitor tucatinib when added to trastuzumab and capecitabine was shown to improve PFS and overall survival (OS) over trastuzumab and capecitabine alone in pretreated patients in the randomized HER2CLIMB trial; this benefit was apparently independent of hormone-receptor expression. An update from the DESTINY-Breast01 trial reported a median PFS of 19.4 months with trastuzumab deruxtecan in heavily pretreated patients. Finally, an analysis from the PERTAIN trial with > 6 years median follow-up showed excellent OS in patients with luminal B/HER2-positive receiving first-line trastuzumab/pertuzumab in combination with endocrine therapy suggesting that chemotherapy-free treatment is an option in highly selected patients.

scholarly journals Estrogen Receptor Positive Breast Cancer with High Expression of Androgen Receptor has Less Cytolytic Activity and Worse Response to Neoadjuvant Chemotherapy but Better Survival

2019 ◽  
Vol 20 (11) ◽  
pp. 2655 ◽  
Author(s):  
Maiko Okano ◽  
Masanori Oshi ◽  
Ali Linsk Butash ◽  
Mariko Asaoka ◽  
Eriko Katsuta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Cytolytic Activity ◽  
Er Positive ◽  
Infiltrating Lymphocytes ◽  
Response To Neoadjuvant Chemotherapy ◽  
Positive Breast Cancer

Estrogen receptor (ER) positive breast cancer (BC), the most abundant BC subtype, is notorious for poor response to neoadjuvant chemotherapy (NAC). The androgen receptor (AR) was reported to support estradiol-mediated ER activity in an in vitro system. Recently, ER-positive BC with fewer tumor infiltrating lymphocytes (TILs) was shown to have a better prognosis, opposite to the trend seen with ER-negative BC. We hypothesized that ER-positive BC with high expression of AR will have fewer TILs and an inferior response to NAC, but with a better prognosis. In both TCGA and METABRIC cohorts, AR expression was significantly higher in ER-positive BCs compared to ER-negatives (p < 0.001, p < 0.001, respectively) and it correlated with ER expression (R = 0.630, R = 0.509, respectively). In ER-positive tumors, AR high tumors enriched UV response down (NES = 2.01, p < 0.001), and AR low tumors enriched DNA repair (NES = −2.02, p < 0.001). AR high tumors were significantly associated with procancer regulatory T-cells, and AR low tumors were associated with anticancer immune cells, such as CD4, CD8, and Gamma-Delta T-cells and memory B-cells in ER-positive BC (p < 0.01). Further, cytolytic activity was significantly lower in AR high BC in both cohorts. Finally, AR high tumors had a significantly lower rate of attaining pathological complete response to NAC (GSE22358), but better survival. In conclusion, our results demonstrated that high AR has fewer tumor infiltrating lymphocytes as well as cytolytic activity and an inferior response to NAC, but better survival in ER-positive BC.

Sign in / Sign up

Export Citation Format

Share Document