Impact of oligometastatic disease on survival in ER positive breast cancer: A population-based analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19109-e19109
Author(s):  
Nathalie LeVasseur ◽  
Kaylie Willemsma ◽  
Caroline A. Lohrisch ◽  
Nafisha Lalani ◽  
Stephen K. L. Chia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Real World ◽  
Treatment Modalities ◽  
Clinical Equipoise ◽  
Breast Cancer Patients ◽  
Oligometastatic Disease ◽  
Er Positive ◽  
The Impact ◽  
Positive Breast Cancer

e19109 Background: Estrogen positive (ER) advanced breast cancers (ABC) are associated with a longer survival compared to other subtypes. However, clinical equipoise remains for the management of oligometastatic disease. While recent phase I and II data support the use of metastasis-directed therapy, breast cancer patients remain underrepresented and real-world outcomes for breast cancer patients with directed treatment for oligometastases is lacking. Methods: The BC Cancer Breast Cancer Outcomes Unit (BCOU) database was utilized to identify patients with ER positive breast cancer referred to BC Cancer from 2005-2014 with documented metastases. Baseline clinical, pathological and treatment data were compiled. Overall survival (OS) was compared between the group with oligometastatic disease(OM) (defined as < = 5 foci of metastases) and the group with non-oligometastatic disease (defined as > = 6 foci of metastases) using Kaplan-Meier survival curves. Key secondary endpoints included metastasis-directed treatment impact, based on the site of metastasis, local control (LC) and distant failure (DF) rate. Results: A total of 938 patients met the inclusion criteria. Of these, 191 (20.4%) had OM and 747 (79.6%) had widespread disease at 1st diagnosis of ABC. The groups were well balanced for clinical characteristics (all p > 0.05), with a median age of 59yrs (23-99). 84% were ductal carcinomas, 14% were also HER2 positive. Sites of oligometastases were bone (66.5%), liver (12.0%), brain (8.4%) and lung (5.8%). Median follow-up was 7.4 yrs. Median OS was 24 mo (95% CI 20.2, 27.8) for patients with OM and 11 mo (9.5, 12.5) for those with widespread disease (p < 0.0001). In the OM group, 114 (59.7%) of patients received metastasis-directed treatment, whereas 77 (40.3%) did not. Treatment modalities included radiation in 53.4% of patients, surgery in 8.9% of patients and stereotactic body radiotherapy (SBRT) in 3.7%. Median OS was 24 mo (18.3, 29.7) for patients who received metastasis-directed treatment and 23 mo (17.5, 28.5) for those who did not (p = 0.954). Patients with bone-only metastases had a median OS of 27mo with directed treatment and 25mo without directed-treatment (p = 0.334). Conclusions: Oligometastatic state was associated with a significantly better OS. Metastasis-directed treatment was associated with a non-significant OS difference in patients with bone-only metastases in a real world cohort. However, the impact of modern systemic treatment and SBRT methods are evolving. Large prospective randomized studies of this approach merit further study.

scholarly journals Clinical CYP2D6 Genotyping to Personalize Adjuvant Tamoxifen Treatment in ER-Positive Breast Cancer Patients: Current Status of a Controversy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 771
Author(s):  
Tessa A. M. Mulder ◽  
Mirjam de With ◽  
Marzia del Re ◽  
Romano Danesi ◽  
Ron H. J. Mathijssen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Plasma Concentrations ◽  
Tamoxifen Treatment ◽  
Current Status ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

Tamoxifen is a major option for adjuvant endocrine treatment in estrogen receptor (ER) positive breast cancer patients. The conversion of the prodrug tamoxifen into the most active metabolite endoxifen is mainly catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). Genetic variation in the CYP2D6 gene leads to altered enzyme activity, which influences endoxifen formation and thereby potentially therapy outcome. The association between genetically compromised CYP2D6 activity and low endoxifen plasma concentrations is generally accepted, and it was shown that tamoxifen dose increments in compromised patients resulted in higher endoxifen concentrations. However, the correlation between CYP2D6 genotype and clinical outcome is still under debate. This has led to genotype-based tamoxifen dosing recommendations by the Clinical Pharmacogenetic Implementation Consortium (CPIC) in 2018, whereas in 2019, the European Society of Medical Oncology (ESMO) discouraged the use of CYP2D6 genotyping in clinical practice for tamoxifen therapy. This paper describes the latest developments on CYP2D6 genotyping in relation to endoxifen plasma concentrations and tamoxifen-related clinical outcome. Therefore, we focused on Pharmacogenetic publications from 2018 (CPIC publication) to 2021 in order to shed a light on the current status of this debate.

scholarly journals Analysis of ESR1 and PIK3CA mutations in plasma cell-free DNA from ER-positive breast cancer patients

Oncotarget ◽  
2017 ◽  
Vol 8 (32) ◽  
pp. 52142-52155 ◽  
Author(s):  
Takashi Takeshita ◽  
Yutaka Yamamoto ◽  
Mutsuko Yamamoto-Ibusuki ◽  
Mai Tomiguchi ◽  
Aiko Sueta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Plasma Cell ◽  
Breast Cancer Patients ◽  
Cell Free Dna ◽  
Pik3ca Mutations ◽  
Free Dna ◽  
Er Positive ◽  
Positive Breast Cancer

Comparing practice patterns and outcomes for early-stage hormone receptor-positive and node-positive breast cancer patients with high-intermediate-risk Oncotype Dx scores in the National Cancer Database.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12520-e12520
Author(s):  
Keerthi Tamragouri ◽  
Ethan M. Ritz ◽  
Ruta D. Rao ◽  
Cristina O'Donoghue
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Predictive Value ◽  
Practice Patterns ◽  
Early Stage ◽  
Oncotype Dx ◽  
Breast Cancer Patients ◽  
Node Positive ◽  
The Impact ◽  
Positive Breast Cancer

e12520 Background: Oncotype Dx (ODX) is a commercial diagnostic test primarily used to predict the likely benefit from chemotherapy in ER+, HER2-, and node negative breast cancer. The prognostic value (recurrence risk) has also been demonstrated to apply to early stage lymph node positive (LN+) disease in a number of retrospective and prospective studies. The ongoing RxPONDER trial aims to clarify the predictive value of RS in LN+ population. In light of the initial results, we analyzed the practice patterns and outcomes for HR+/Her2 -/node positive breast cancer patients receiving ODX testing in the years from 2010-2017 with RS 14-25 in a retrospective observational study of the NCDB. Methods: Women with HR+/Her2 -/node positive breast cancer receiving ODX testing from 2010-2017 were identified in the NCDB using TAILORx and RxPONDER patients’ inclusion criteria: ages 18-75, 6-50mm invasive tumors, N1, M0, ER+/HER2 -. The impact of ODX results in the high-intermediate range (14-25) and other clinico-pathologic variables on the receipt of chemotherapy were compared. Additionally, we examined the impact of chemotherapy on overall survival (OS). Frequencies, Kaplain-Meier analysis, and changepoint analysis using the Contal and O’Quigley method were utilized. Results: There were 109,652 T1-2 and N1 patients of whom 32,506 (29.6%) received ODX testing. 13,461 (41.4%%) women had scores in the high-intermediate (14-25) range. The majority tended to have only 1 LN involved (1LN: 77.2%, 2LNs: 17.5%, 3LNs: 5.3%), had a mean age of 57.8y, were Caucasian (86.4%), and were preferentially tested at academic or comprehensive community cancer programs (79.2%). 6,610 (49.3%) patients were recommended chemotherapy, the median ODX score for all women who were recommended chemotherapy was 20 compared to 17 for those whom chemotherapy was not recommended. 5,068 (76.7%) women had documentation of receiving chemotherapy which correlated with improved OS regardless of age. Conclusions: In the group of women with HR+/Her2 -/node positive breast cancer, clinicians appear to utilize ODX testing in less than one-third of patients, possibly finding RS to be most useful in guiding adjuvant therapy recommendations when only 1LN is involved. Both the recommendation and receipt of chemotherapy correlated linearly with increasing RS, as expected based on the current NCCN guideline recommendations. We identified an OS benefit when chemotherapy was administered, regardless of patient age. Long-term follow-up in the RxPONDER trial will likely continue to clarify the predictive value of RS < 25 in the ER+/HER2-/node positive breast cancer population.

Preoperative hormonal therapy vs chemotherapy in postmenopausal ER-positive breast cancer patients

2004 ◽  
Vol 2 (3) ◽  
pp. 71 ◽  
Author(s):  
V.F Semiglazov ◽  
V.V Semiglazov ◽  
V.G Ivanov ◽  
E.K Ziltsova ◽  
G.A Dashian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Hormonal Therapy ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

scholarly journals ESR1-Stabilizing Long Noncoding RNA TMPO-AS1 Promotes Hormone-Refractory Breast Cancer Progression

2019 ◽  
Vol 39 (23) ◽  
Author(s):  
Yuichi Mitobe ◽  
Kazuhiro Ikeda ◽  
Takashi Suzuki ◽  
Kiyoshi Takagi ◽  
Hidetaka Kawabata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Cancer Progression ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

ABSTRACT Acquired endocrine therapy resistance is a significant clinical problem for breast cancer patients. In recent years, increasing attention has been paid to long noncoding RNA (lncRNA) as a critical modulator for cancer progression. Based on RNA-sequencing data of breast invasive carcinomas in The Cancer Genome Atlas database, we identified thymopoietin antisense transcript 1 (TMPO-AS1) as a functional lncRNA that significantly correlates with proliferative biomarkers. TMPO-AS1 positivity analyzed by in situ hybridization significantly correlates with poor prognosis of breast cancer patients. TMPO-AS1 expression was upregulated in endocrine therapy-resistant MCF-7 cells compared with levels in parental cells and was estrogen inducible. Gain and loss of TMPO-AS1 experiments showed that TMPO-AS1 promotes the proliferation and viability of estrogen receptor (ER)-positive breast cancer cells in vitro and in vivo. Global expression analysis using a microarray demonstrated that TMPO-AS1 is closely associated with the estrogen signaling pathway. TMPO-AS1 could positively regulate estrogen receptor 1 (ESR1) mRNA expression by stabilizing ESR1 mRNA through interaction with ESR1 mRNA. Enhanced expression of ESR1 mRNA by TMPO-AS1 could play a critical role in the proliferation of ER-positive breast cancer. Our findings provide a new insight into the understanding of molecular mechanisms underlying hormone-dependent breast cancer progression and endocrine resistance.

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