First report of the European Cooperative Trial in Operable Breast Cancer II (ECTO II): Effects of primary chemo-endocrine therapy on local-regional disease in ER-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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Is primary endocrine therapy effective in treating the elderly, unfit patient with breast cancer?

Annals of The Royal College of Surgeons of England ◽

10.1308/003588411x571917 ◽

2011 ◽

Vol 93 (4) ◽

pp. 286-289 ◽

Cited By ~ 7

Author(s):

G Osborn ◽

M Jones ◽

C Champ ◽

K Gower-Thomas ◽

E Vaughan-Williams

Keyword(s):

Breast Cancer ◽

Disease Progression ◽

Endocrine Therapy ◽

General Anaesthetic ◽

Number Of Patients ◽

Co Morbidity ◽

Er Positive ◽

Primary Endocrine Therapy ◽

Positive Breast Cancer

INTRODUCTION Elderly patients with oestrogen receptor (ER)-positive breast cancer wishing to avoid surgery or those who are considered unsuitable for a general anaesthetic may be treated with primary endocrine therapy. We have reviewed all patients with ER-positive breast cancer who were initially treated with primary hormone therapy (PHT) at a district general hospital in south Wales and investigated their outcome in order to evaluate the appropriateness of this method of managing breast cancer. MATERIALS AND METHODS All patients with breast cancer who were initially treated with PHT between January 2002 and December 2008 were identified from a single consultant's prospectively maintained database. For each patient the Charlson co-morbidity index was calculated to give an estimate of ten-year survival. Patients who had died during the study period were identified from hospital and cancer registries. RESULTS A total of 83 cancers in 82 patients with a median age of 81 years (range: 62–93 years) were included. All cancers were ER-positive. Six patients (7%) had a greater than 50% chance of surviving ten years, calculated using the Charlson index. The median follow-up period was 24 months (range: 6–72 months). Twelve patients (15%) had disease progression while taking PHT. Twenty-three patients (28%) have died (median time from diagnosis to death of 10.5 months, range: 1–77 months). Two patients (2%) experienced disease progression within six months of starting PHT and the number of patients whose cancer progressed increased with increasing length of follow up. Fourteen patients (17%) eventually underwent a wide local excision under local anaesthetic. CONCLUSIONS PHT can be considered an effective treatment in this elderly, unfit population with the aim of stopping disease progression so that these patients die with their breast cancer, not of it.

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Adjuvant CMFVP versus tamoxifen versus concurrent CMFVP and tamoxifen for postmenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.10.2078 ◽

1994 ◽

Vol 12 (10) ◽

pp. 2078-2085 ◽

Cited By ~ 68

Author(s):

S E Rivkin ◽

S Green ◽

B Metch ◽

A B Cruz ◽

M D Abeloff ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Postmenopausal Women ◽

Eastern Cooperative Oncology Group ◽

Operable Breast Cancer ◽

Oncology Group ◽

Southwest Oncology Group ◽

Node Positive ◽

Er Positive ◽

Positive Breast Cancer

PURPOSE To compare chemohormonal therapy, chemotherapy alone, and hormonal therapy alone in postmenopausal patients with estrogen receptor (ER)-positive operable breast cancer and positive axillary nodes with respect to survival and disease-free survival (DFS). PATIENTS AND METHODS Eight hundred ninety-two postmenopausal women with ER-positive, node-positive breast cancer were enrolled by the Southwest Oncology Group (SWOG) from July 1979 to March 1989 and 74 by the Eastern Cooperative Oncology Group (ECOG) between June 1987 and March 1989. Patients were stratified according to number of involved nodes and type of primary surgery and randomized to receive the following: (1) tamoxifen 10 mg twice daily by mouth for 1 year; (2) cyclophosphamide 60 mg/m2/d by mouth for 1 year, methotrexate 15 mg/m2 intravenously (IV) weekly for 1 year, fluorouracil (5-FU) 400 mg/m2 IV weekly for 1 year, vincristine .625 mg/m2 IV weekly for the first 10 weeks, and prednisone during weeks 1 to 10 with doses decreasing from 30 mg/m2 to 2.5 mg/m2 (CMFVP); or (3) the combination of tamoxifen and CMFVP. RESULTS The median follow-up duration is 6.5 years, with a maximum of 12.8 years. Treatment arms are not significantly different with respect to either survival or DFS (log-rank, 2 df, P = .82 and .23, respectively). The 5-year survival rate is 77% for the tamoxifen arm, 78% for CMFVP, and 75% for the combination. No significant differences were observed in node or receptor level subsets. Severe or worse toxicity was experienced by 56% of patients on CMFVP and 61% on CMFVP plus tamoxifen, compared with 5% on tamoxifen alone. CONCLUSION CMFVP chemotherapy, either alone or in combination with tamoxifen, has not been shown to be superior to tamoxifen alone in the treatment of postmenopausal women with node-positive, ER-positive, operable breast cancer.

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