Estrogen for the Treatment and Prevention of Breast Cancer: A Tale of 2 Karnofsky Lectures.

In 1971, Sir Alexander Haddow et al. delivered the inaugural David A. Karnofsky lecture at the American Society for Clinical Oncology.

Estrogen Receptor Complex to Trigger or Delay Estrogen-Induced Apoptosis in Long-Term Estrogen Deprived Breast Cancer.

Antiestrogen therapy of breast cancer has been a "gold standard" of treatment of estrogen receptor (ER)-positive breast cancer for decades. Resistance to antiestrogen therapy may develop, however, a vulnerability in long-term estrogen deprived (LTED) breast cancer cells was discovered. LTED breast cancer cells may undergo estrogen-induced apoptosis within a week of treatment with estrogen .

Downregulation of 15-hydroxyprostaglandin dehydrogenase during acquired tamoxifen resistance and association with poor prognosis in ERα-positive breast cancer.

Aim: Tamoxifen (TAM) resistance remains a clinical issue in breast cancer. The authors previously reported that 15-hydroxyprostaglandin dehydrogenase () was significantly downregulated in tamoxifen-resistant (TAMr) breast cancer cell lines. Here, the authors investigated the relationship between HPGD expression, TAM resistance and prediction of outcome in breast cancer.

Rapid Induction of the Unfolded Protein Response and Apoptosis by Estrogen Mimic TTC-352 for the Treatment of Endocrine-Resistant Breast Cancer.

Patients with long-term estrogen-deprived breast cancer, after resistance to tamoxifen or aromatase inhibitors develops, can experience tumor regression when treated with estrogens. Estrogen's antitumor effect is attributed to apoptosis via the estrogen receptor (ER). Estrogen treatment can have unpleasant gynecologic and nongynecologic adverse events; thus, the development of safer estrogenic agents remains a clinical priority.

Pharmacology and Molecular Mechanisms of Clinically Relevant Estrogen Estetrol and Estrogen Mimic BMI-135 for the Treatment of Endocrine-Resistant Breast Cancer.

Long-term estrogen deprivation (LTED) with tamoxifen (TAM) or aromatase inhibitors leads to endocrine-resistance, whereby physiologic levels of estrogen kill breast cancer (BC). Estrogen therapy is effective in treating patients with advanced BC after resistance to TAM and aromatase inhibitors develops. This therapeutic effect is attributed to estrogen-induced apoptosis via the estrogen receptor (ER).

The Structure-Function Relationship of Angular Estrogens and Estrogen Receptor Alpha to Initiate Estrogen-Induced Apoptosis in Breast Cancer Cells.

High-dose synthetic estrogen therapy was the standard treatment of advanced breast cancer for three decades until the discovery of tamoxifen. A range of substituted triphenylethylene synthetic estrogens and diethylstilbestrol were used. It is now known that low doses of estrogens can cause apoptosis in long-term estrogen deprived (LTED) breast cancer cells resistant to antiestrogens.

Early career interview: Balkees Abderrahman.

Balkees Abderrahman is the Dallas/Ft Worth Living Legend Fellow of Cancer Research at MD Anderson Cancer Center (TX, USA) and split-site PhD candidate under Model 'Individuals of Very High Quality' at the University of Leeds (UK), where she studies cancer. She was one of three finalists of the 2019 Future Science Future Star Award. Here, she tells us about her career to-date.

Suppression of Nuclear Factor-κB by Glucocorticoid Receptor Blocks Estrogen-Induced Apoptosis in Estrogen-Deprived Breast Cancer Cells.

Our clinically relevant finding is that glucocorticoids block estrogen (E)-induced apoptosis in long-term E-deprived (LTED) breast cancer cells. However, the mechanism remains unclear. Here, we demonstrated that E widely activated adipose inflammatory factors such as fatty acid desaturase 1 (FADS1), IL6, and TNFα in LTED breast cancer cells.

Targeting Peroxisome Proliferator-Activated Receptor γ to Increase Estrogen-Induced Apoptosis in Estrogen-Deprived Breast Cancer Cells.

Peroxisome proliferator-activated receptor γ (PPARγ) is an important transcription factor that modulates lipid metabolism and inflammation. However, it remains unclear whether PPARγ is involved in modulation of estrogen (E)-induced inflammation, thus affecting apoptosis of E-deprived breast cancer cells, MCF-7:5C and MCF-7:2A. Here, we demonstrated that E treatment suppressed the function of PPARγ in both cell lines, although the suppressive effect in MCF-7:2A cells was delayed owing to high PPARγ expression.

Successful Targeted Therapies for Breast Cancer: the Worcester Foundation and Future Opportunities in Women's Health.

The signing of the National Cancer Act in 1971 was designed to take laboratory discoveries rapidly from the bench to the bedside. A "war on cancer" had been declared. Combination cytotoxic chemotherapy was predicted to cure all cancers, based on the stunning success in treating childhood leukemia.

Endoxifen, 4-Hydroxytamoxifen and an Estrogenic Derivative Modulate Estrogen Receptor Complex Mediated Apoptosis in Breast Cancer.

Estrogen therapy was used to treat advanced breast cancer in postmenopausal women for decades until the introduction of tamoxifen. Resistance to long-term estrogen deprivation (LTED) with tamoxifen and aromatase inhibitors used as a treatment of breast cancer inevitably occurs, but unexpectedly low-dose estrogen can cause regression of breast cancer and increase disease-free survival in some patients. This therapeutic effect is attributed to estrogen-induced apoptosis in LTED breast cancer.

A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers.

Prostate and breast cancer are the two cancers with the highest incidence in men and women, respectively. Here, we focus on the known biology of acquired resistance to antihormone therapy of prostate and breast cancer and compare laboratory and clinical similarities in the evolution of the disease. Laboratory studies and clinical observations in prostate and breast cancer demonstrate that cell selection pathways occur during acquired resistance to antihormonal therapy.

Opportunities and challenges of long term anti-estrogenic adjuvant therapy: treatment forever or intermittently?

Extended adjuvant (5-10 years) therapy targeted to the estrogen receptor (ER) has significantly decreased mortality from breast cancer (BC). Areas covered: Translational research advanced clinical testing of extended adjuvant therapy with tamoxifen or aromatase inhibitors (AIs). Short term therapy or non-compliance increase recurrence, but surprisingly recurrence and death does not increase dramatically after 5 years of adjuvant therapy stops.

Sex steroid induced apoptosis as a rational strategy to treat anti-hormone resistant breast and prostate cancer.

The combined incidence and the extended disease course of breast and prostate cancer is a major challenge for health care systems. The solution for society requires an economically viable treatment strategy to maintain individuals disease free and productive, so as to avoid the fracture of the family unit. Forty years ago, translational research using the antiestrogen tamoxifen was targeted to estrogen receptor (ER) positive micrometastatic tumor cells and established the long-term antihormone adjuvant treatment strategy used universally today.