The Omission of Endocrine Therapy (ET) in Older Women with Stage I Estrogen-Receptor (ER)-Positive Breast Cancer Is Not Associated with a Higher Risk of Recurrence

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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Patterns of relapse in older women diagnosed with estrogen receptor (ER)–positive early-stage breast cancer (BC) treated with lumpectomy without adjuvant endocrine therapy (ET)

Journal of Radiation Oncology ◽

10.1007/s13566-019-00405-y ◽

2019 ◽

Vol 8 (3) ◽

pp. 349-353

Author(s):

Manjeet Chadha ◽

T. Shao ◽

S. Cate ◽

S. Malamud ◽

C. White ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Older Women ◽

Endocrine Therapy ◽

Early Stage ◽

Adjuvant Endocrine Therapy ◽

Early Stage Breast Cancer ◽

Er Positive

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Controversies in Adjuvant Endocrine Therapy for Breast Cancer

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2012.32.87 ◽

2012 ◽

pp. 20-26

Author(s):

Stephen R. Johnston

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Aromatase Inhibitors ◽

Early Stage ◽

Premenopausal Women ◽

Adjuvant Endocrine Therapy ◽

Risk Of Recurrence ◽

Er Positive ◽

Added Benefit ◽

Positive Breast Cancer

Overview: Adjuvant endocrine therapy for early-stage breast cancer has had the single biggest impact on improving survival from the disease—with tamoxifen alone contributing to saving many thousands of lives. In postmenopausal women, additional progress has been made by the incorporation of aromatase inhibitors into the treatment of early-stage, estrogen receptor (ER)–positive breast cancer, as several large well-conducted trials have established either “up-front” or “switch” strategies that are now widely used. To date, both have been shown to be beneficial when compared with tamoxifen alone, although controversy exists as to which approach is superior. Increasingly, extended adjuvant therapy is being considered, as “longer may be better” for some women who have an ongoing risk of recurrence beyond 5 years. However, controversy remains as to how long adjuvant endocrine therapy should be given for; in clinical practice, clinicians balance the level of risk for individual patients versus any ongoing toxicity concerns. For premenopausal women, with ER-positive breast cancer, tamoxifen remains the gold standard with uncertainty in the added overall benefit of ovarian suppression. Important clinical trials have recently been completed that may help answers this question, including whether complete estrogen deprivation using a luteinizing hormone releasing hormone (LHRH) agonist plus aromatase inhibitors (AIs) is of added benefit. In recent years, molecular profiling of ER-positive breast cancer has started to distinguish those women with a low risk of recurrence on endocrine therapy who may not need chemotherapy. Thus, with more therapy options and greater tumour stratification, modern, adjuvant endocrine therapy is becoming increasingly personalised to suit each individual patient's risk.

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Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in estrogen receptor-positive breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e21160 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e21160-e21160

Author(s):

Ji sun Kim ◽

Wonshik Han ◽

Jee Man You ◽

Hee-Chul Shin ◽

Soo Kyung Ahn ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Endocrine Therapy ◽

Breast Density ◽

Adjuvant Endocrine Therapy ◽

Absolute Difference ◽

Mammographic Breast Density ◽

Short Term ◽

Er Positive ◽

Positive Breast Cancer

e21160 Background: Previous studies showed that anti-estrogen therapy lowers mammographic breast density (MD). We hypothesized that the short-term change of breast density can be a surrogate marker predicting response to adjuvant endocrine therapy (ET) for breast cancer. Methods: We analyzed data of 1,065 estrogen receptor (ER)-positive breast cancer patients who underwent surgery between 2003 and 2006 and received at least 2 years of ET including tamoxifen and aromatase inhibitor. MD was measured using Cumulus software 4.0 and expressed as a percentage. MD reduction was defined as an absolute difference between the MD of two mammography images: taken preoperatively and 8-20months after the start of adjuvant ET.. Results: After median follow up of 68.8 months, overall recurrence rate was 7.5% (80/1065). Mean MD reduction was 5.9% (-17.2 to 36.9). In a logistic regression analysis, age<50, high preoperative MD, and longer interval between start of ET to the 2nd mammogram were significantly associated with higher MD reduction (p value<0.05). In a survival analysis using Cox model, tumor size (>2cm), lymph node positive, high Ki-67 (≥10%), and lower MD reduction were independent factors significantly associated with recurrence-free survival (p<0.05). The hazard of recurrence increased proportionally according to the less degree of MD reduction. Conclusions: MD change during short-term use of adjuvant ET was a significant predictive factor for long-term recurrence in ER-positive breast cancer. It is urgent to develop effective treatment strategy in patients who have less MD reduction in spite of about 1 year of ET.

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Abstract P5-13-02: Neoadjuvant endocrine therapy for estrogen receptor (ER) positive breast cancer: Comprehensive systematic review and meta-analysis

10.1158/1538-7445.sabcs15-p5-13-02 ◽

2016 ◽

Author(s):

L Spring ◽

A Gupta ◽

KL Reynolds ◽

MA Gadd ◽

SJ Isakoff ◽

...

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Estrogen Receptor ◽

Endocrine Therapy ◽

Meta Analysis ◽

Neoadjuvant Endocrine Therapy ◽

Er Positive ◽

Positive Breast Cancer

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Stat5 expression predicts response to endocrine therapy and improves survival in estrogen receptor-positive breast cancer

Endocrine Related Cancer ◽

10.1677/erc.1.01095 ◽

2006 ◽

Vol 13 (3) ◽

pp. 885-893 ◽

Cited By ~ 56

Author(s):

H Yamashita ◽

M Nishio ◽

Y Ando ◽

Z Zhang ◽

M Hamaguchi ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Epithelial Cell ◽

Endocrine Therapy ◽

Histological Grade ◽

Metastatic Breast ◽

Therapy Response ◽

Breast Cancer Patients ◽

Er Positive ◽

Positive Breast Cancer

Constitutively activated signal transducers and activators of transcription (Stats), in particular Stat3 and Stat5, have been demonstrated to directly contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis in various cancers. Stat3 is essential in mammary gland epithelial cell apoptosis and involution, whereas Stat5 is well established as a key factor in mammary epithelial cell growth and differentiation. Crosstalk between Stats and estrogen receptor (ER) has been demonstrated by several laboratories and we have focused on the role of Stat5 in ER-positive breast cancer. Using immunohistochemical techniques, we examined the expression of Stat3 and Stat5 in 517 human breast cancer tissues and analyzed their significance for prognosis and prediction of response to endocrine therapy. Stat5 expression was significantly correlated with histological grade (P < 0.0001), ER (P = 0.02), and progesterone receptor (P = 0.026) expression. There was no difference between Stat3 expression and clinicopathological factors. In 346 patients with ER-positive breast cancer, patients with Stat5 positive tumors had significantly increased overall survival (P = 0.0009) in multivariate analysis. There were 70 patients who received endocrine therapy as first-line treatment for metastatic breast cancer at relapse. The patients whose primary breast tumors were Stat5 positive, had significantly better response to endocrine therapy (P = 0.04), and longer survival after relapse (P = 0.0003), than those whose tumors were Stat5 negative. The present study demonstrates for the first time that Stat5 is a predictive factor for endocrine therapy response and a strong prognostic molecular marker in ER-positive breast cancer. Our data suggest that the expression of Stat5 is helpful in selecting patients who may benefit from endocrine therapy.

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Predictors of Tamoxifen Discontinuation Among Older Women With Estrogen Receptor–Positive Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.10.1022 ◽

2008 ◽

Vol 26 (4) ◽

pp. 549-555 ◽

Cited By ~ 204

Author(s):

Cynthia Owusu ◽

Diana S.M. Buist ◽

Terry S. Field ◽

Timothy L. Lash ◽

Soe Soe Thwin ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Older Women ◽

Proportional Hazards ◽

Care Delivery ◽

Breast Conserving Surgery ◽

Cox Proportional Hazards ◽

Adjuvant Tamoxifen ◽

Er Positive ◽

Positive Breast Cancer

Purpose Five years of adjuvant tamoxifen therapy for estrogen receptor (ER) –positive breast cancer is more effective than 2 years of use. However, information on tamoxifen discontinuation is scanty. We sought to identify predictors of tamoxifen discontinuation among older women with breast cancer. Patients and Methods Within six health care delivery systems, we identified women ≥ 65 years old diagnosed with stage I to IIB ER-positive or indeterminant breast cancer between 1990 and 1994 who had filled a prescription for adjuvant tamoxifen. We observed them for 5 years after initial tamoxifen prescription. We used automated pharmacy records to validate tamoxifen prescription information abstracted from medical records. The primary end point was tamoxifen discontinuation, operationalized as ever discontinuing tamoxifen during 5 years of follow-up. We used Cox proportional hazards to identify predictors of tamoxifen discontinuation. Results Of 961 women who were prescribed tamoxifen, 49% discontinued tamoxifen before the completion of 5 years. Discontinuers were more likely to be aged 75 to less than 80 years (v < 70 years; hazard ratio [HR] = 1.41; 95% CI, 1.06 to 1.87), be aged ≥ 80 years (HR = 2.02; 95% CI, 1.53 to 2.66), have an increase in Charlson Comorbidity Index at 3 years from diagnosis (HR = 1.52; 95% CI, 1.18 to 1.95), have an increase in the number of cardiopulmonary comorbidities at 3 years (HR = 1.75; 95% CI, 1.34 to 2.28), have indeterminant ER status (v ER-positive status; HR = 1.36; 95% CI, 1.00 to 1.85), and have received breast-conserving surgery (BCS) without radiotherapy (v mastectomy; HR = 1.62; 95% CI, 1.18 to 2.22). Conclusion Attention to nonadherence among older women at risk of discontinuation, particularly those receiving BCS without radiotherapy, might improve breast cancer outcomes for these women.

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