Related Experiment Videos
[Endocrine therapy for advanced or recurrent breast cancer]
1Department of Breast and Thyroid Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan.
Abstract:
Endocrine therapy of advanced or recurrent breast cancer was described. The presence of ER or PgR in primary breast tumors is the best-established marker for response to endocrine therapy. However, ER-positive breast tumors overexpressing EGF-R and/or HER-2 (Erb B2) are resistant to endocrine therapy. Recently it was suggested that an elevated level of the circulating extracellular domain of HER-2 could be a predictor for poor response to endocrine therapy. LH-RH agonist is used as a first-line therapy for premenopausal patients. And LH-RH agonist plus tamoxifen (TAM) has shown a higher response rate and more prolonged survival than LH-RH agonist or TAM alone. As two new aromatase inhibitors, anastrozole (ANA) and letrozole, have shown an equal or higher response rate and a prolonged time to progression than TAM as a first-line therapy, these could be used as a first-line therapy instead of TAM. In a cross-over trial of ANA and TAM, the response rate of ANA after TAM failure was equal to that of TAM after ANA failure. As these drugs showed an equal or higher response rate and longer survival than progestin in TAM resistant cases, these drugs could also used as a second-line therapy. In addition, the trend of recent studies regarding the mechanisms of hormone resistance is also described.
Insights
Endocrine therapy for advanced breast cancer shows varying response rates. Overexpression of HER-2 (Erb B2) can lead to resistance, but new aromatase inhibitors like anastrozole (ANA) and letrozole offer improved outcomes.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Context:
- Estrogen receptor (ER) and progesterone receptor (PgR) status are key predictors for endocrine therapy response in breast cancer.
- ER-positive breast tumors with overexpression of EGF-R and/or HER-2 (Erb B2) often exhibit resistance to standard endocrine treatments.
- Elevated levels of circulating HER-2 extracellular domain may indicate a poorer response to endocrine therapy.
Purpose:
- To review current endocrine therapy strategies for advanced or recurrent breast cancer.
- To discuss the role of HER-2 (Erb B2) overexpression and circulating HER-2 levels as predictors of endocrine therapy resistance.
- To evaluate the efficacy of luteinizing hormone-releasing hormone (LH-RH) agonists and aromatase inhibitors (anastrozole [ANA], letrozole) in breast cancer treatment.
Summary:
- LH-RH agonists are a first-line option for premenopausal patients, with combination therapy (LH-RH agonist plus tamoxifen [TAM]) showing enhanced response and survival.
- Anastrozole (ANA) and letrozole demonstrate comparable or superior response rates and prolonged progression-free survival compared to TAM as first-line therapy.
- These aromatase inhibitors are also effective as second-line therapies in tamoxifen-resistant cases, showing improved outcomes over progestin.
- Recent research trends in understanding hormone resistance mechanisms are also covered.
Impact:
- Identifies predictive markers (ER, PgR, HER-2) for endocrine therapy response in advanced breast cancer.
- Highlights the clinical utility of LH-RH agonists and novel aromatase inhibitors (anastrozole, letrozole) in first- and second-line settings.
- Provides insights into managing endocrine resistance and informs future therapeutic strategies for breast cancer.