Doctors prescribe drugs known as CDK inhibitors to treat some women with estrogen-receptor-positive (ER+) metastatic breast cancer. Research into these drugs is ongoing, and new, promising CDK inhibitor options are on the horizon. Here, I address the current outlook for CDK inhibitors in ER+ breast cancer.
First, some background: ER+ breast cancers comprise about 70% of all breast cancers. The name reflects the fact that cells of these cancers express estrogen receptors (ERs), which are protein features targeted by many treatment strategies for this cancer type. The estrogen receptor (ER) protein is a treatment target not only because “it is there,” but mainly because it drives tumor cell proliferation in ER+ breast cancer. The activity of the ER depends on its binding to the hormone estrogen, and treatments known as endocrine drugs aim to prevent this interaction. Some endocrine drugs inhibit the synthesis of estrogen in the body (e.g., aromatase inhibitors, such as letrozole and anastrozole), and others prevent the interaction of estrogen with ERs (e.g., ER modulators such as tamoxifen, or the pure anti-estrogen drug fulvestrant). The problem of course is that, in metastatic breast cancer, resistance develops to each and every endocrine drug used. Continue reading…
“Postmenopausal women with breast cancer who took aromatase inhibitors demonstrated endothelial dysfunction, a predictor of cardiovascular disease, according to study results presented at the 2016 San Antonio Breast Cancer Symposium, held Dec. 6–10.
“Aromatase inhibitors (AIs) are a class of drugs that lower estrogen levels, and have been shown to reduce breast cancer-related mortality in women with locally advanced curative intent estrogen receptor-positive disease, which accounts for 75 percent of breast cancer cases.
“However, estrogen also protects against heart disease, and recent research has suggested that the suppression of estrogen raises the risk of cardiovascular disease, said the study’s lead author, Anne H. Blaes, MD, MS, an associate professor in hematology and oncology at the University of Minnesota.”
“Acupuncture may be a viable treatment for women experiencing hot flashes as a result of estrogen-targeting therapies to treat breast cancer, according to a new study from researchers at the Perelman School of Medicine at the University of Pennsylvania. Hot flashes are particularly severe and frequent in breast cancer survivors, but current FDA-approved remedies for these unpleasant episodes, such as hormone replacement therapies are off-limits to breast cancer survivors because they include estrogen. The results of the study are published this week in the Journal of Clinical Oncology.
” ‘Though most people associate hot flashes with menopause, the episodes also affect many breast cancer survivors who have low estrogen levels and often undergo premature menopause, following treatment with chemotherapy or surgery,’ said lead author Jun J. Mao, MD, MSCE, associate professor of Family Medicine and Community Health. ‘These latest results clearly show promise for managing hot flashes experienced by breast cancer survivors through the use of acupuncture, which in previous studies has also been proven to be an effective treatment for joint pain in this patient population.’ “
Earlier this year, a new treatment option was added to the arsenal for ER-positive breast cancer in postmenopausal women when the U.S. Food and Drug Administration (FDA) approved the combination of letrozole (Femara) and palbociclib (Ibrance). Continue reading…
“Survival among people with lung cancer has been better for women than men, and the findings of a recent study indicate that female hormones may be a factor in this difference. The combination of estrogen plus progesterone and the use of long-term hormone therapy were associated with the most significant improvements in survival.
“The study was designed to explore the influence of several reproductive and hormonal factors on overall survival of women with non-small cell lung cancer (NSCLC). After adjusting for stage of disease at diagnosis, treatment type (surgery or radiation), smoking status, age, race, and education level, the only factor studied that predicted survival after a diagnosis of NSCLC was use of hormone therapy.”
“Androgen deprivation therapy (ADT) was significantly associated with an increased risk for acute kidney injury among men with nonmetastatic prostate cancer, according to study results. ‘Although ADT has been shown to have beneficial effects on prostate cancer progression, serious adverse events can occur during treatment,’ Francesco Lapi, PharmD, PhD, of the Centre for Clinical Epidemiology, Jewish General Hospital, Montreal, and colleagues wrote. ‘By lowering testosterone to castration levels, ADT may antagonize the vasodilating effects of testosterone on renal vessels while also creating an estrogen deficiency, which can negatively affect renal tubular function. Thus, it is possible that through these mechanisms, the use of ADT may increase the risk of acute kidney injury.’ “
International Association for the Study of Lung Cancer | June 24, 2013
Few studies so far have focused specifically on lung cancer in women, despite increasing evidence of differences in lung cancer features between women and men. A striking example is the higher rate among women of nonsmokers who develop lung cancer. A recent study of women with lung adenocarcinoma, a type of non-squamous non-small cell lung cancer (NSCLC), found that those who had never smoked were much more likely to have mutations in the EGFR gene and/or abnormally high levels of estrogen receptors, while smokers were more likely to have mutations in the KRAS gene. Based on these findings, a new phase II clinical trial will explore the effectiveness of treating postmenopausal, nonsmoking women who have advanced non-squamous lung cancer with EGFR inhibitors and anti-estrogen drugs.
Early exposure to the chemical BPA is linked to the development of prostate cancer later in life, according to results from a new clinical study conducted at the University of Illinois in Chicago. BPA is a chemical commonly found in plastic food storage containers, water bottles, and the lining of canned goods, and is thought to act as an estrogen—a hormone that can sometimes promote cancer. To study its effects, researchers implanted mice with developing human prostate cancer cells and fed them BPA in doses similar to what people encounter in their daily lives. The results of the study concluded that mice exposed to BPA had a 33 percent risk of developing prostate cancer, while those not exposed had a 12 percent risk. The chemical is thought to ‘reprogram’ developing prostate cancer cells, making them more susceptible to the cancer causing effects of estrogens later in life.
Langley RE, Cafferty FH, Alhasso AA, Rosen SD, et al. The Lancet Oncology. Mar 4, 2013.
“Luteinising-hormone-releasing-hormone agonists (LHRHa) to treat prostate cancer are associated with long-term toxic effects, including osteoporosis. Use of parenteral oestrogen could avoid the long-term complications associated with LHRHa and the thromboembolic complications associated with oral oestrogen…”