At what age should screening mammography be recommended for Asian women?

Although regular screening mammography has been suggested to be associated with improvements in the relative survival of breast cancer in recent years, the appropriate age to start screening mammography remains controversial. In November 2009, the United States Preventive Service Task Force published updated guidelines for breast cancer, which no longer support routine screening mammography for women aged 40–49 years, but instead, defer the choice of screening in that age group to the patient and physician. The age to begin screening differs between guidelines, including those from the Task Force, the American Cancer Society and the World Health Organization. It remains unclear how this discrepancy impacts patient survival, especially among certain subpopulations. Although the biological characteristics of breast cancer and peak age of incidence differ among different ethnic populations, there have been few reports that evaluate the starting age for screening mammography based on ethnicity. Here, we discuss the benefits and harm of screening mammography in the fifth decade, and re-evaluate the starting age for screening mammography taking ethnicity into account, focusing on the Asian population. Breast cancer incidence peaked in the fifth decade in Asian women, which has been thought to be due to a combination of biological and environmental factors. Previous reports suggest that Asian women in their 40s may receive more benefit and less harm from screening mammography than the age-matched non-Asian US population. Therefore, starting screening mammography at age 40 may be beneficial for women of Asian ethnicity in well-resourced countries, such as Japanese women who reside in Japan

The phosphorylated prodrug FTY720 is a histone deacetylase inhibitor that reactivates ERα expression and enhances hormonal therapy for breast cancer

Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and does not respond to conventional hormonal therapies. Strategies that lead to re-expression of ERα could sensitize ERα-negative breast cancers to selective ER modulators. FTY720 (fingolimod, Gilenya), a sphingosine analog, is the Food and Drug Administration (FDA)-approved prodrug for treatment of multiple sclerosis that also has anticancer actions that are not yet well understood. We found that FTY720 is phosphorylated in breast cancer cells by nuclear sphingosine kinase 2 and accumulates there. Nuclear FTY720-P is a potent inhibitor of class I histone deacetylases (HDACs) that enhances histone acetylations and regulates expression of a restricted set of genes independently of its known effects on canonical signaling through sphingosine-1-phosphate receptors. High-fat diet (HFD) and obesity, which is now endemic, increase breast cancer risk and have been associated with worse prognosis. HFD accelerated the onset of tumors with more advanced lesions and increased triple-negative spontaneous breast tumors and HDAC activity in MMTV-PyMT transgenic mice. Oral administration of clinically relevant doses of FTY720 suppressed development, progression and aggressiveness of spontaneous breast tumors in these mice, reduced HDAC activity and strikingly reversed HFD-induced loss of estrogen and progesterone receptors in advanced carcinoma. In ERα-negative human and murine breast cancer cells, FTY720 reactivated expression of silenced ERα and sensitized them to tamoxifen. Moreover, treatment with FTY720 also re-expressed ERα and increased therapeutic sensitivity of ERα-negative syngeneic breast tumors to tamoxifen in vivo more potently than a known HDAC inhibitor. Our work suggests that a multipronged attack with FTY720 is a novel combination approach for effective treatment of both conventional hormonal therapy-resistant breast cancer and triple-negative breast cancer

Clinical Impact of Sphingosine-1-Phosphate in Breast Cancer

Breast cancer metastasizes to lymph nodes or other organs, which determine the prognosis of patients. It is difficult to cure the breast cancer patients with distant metastasis due to resistance to drug therapies. Elucidating the underlying mechanisms of breast cancer metastasis and drug resistance is expected to provide new therapeutic targets. Sphingosine-1-phosphate (S1P) is a pleiotropic, bioactive lipid mediator that regulates many cellular functions, including proliferation, migration, survival, angiogenesis/lymphangiogenesis, and immune responses. S1P is formed in cells by sphingosine kinases and released from them, which acts in an autocrine, paracrine, and/or endocrine manner. S1P in extracellular space, such as interstitial fluid, interacts with components in the tumor microenvironment, which may be important for metastasis. Importantly, recent translational research has demonstrated an association between S1P levels in breast cancer patients and clinical outcomes, highlighting the clinical importance of S1P in breast cancer. We suggest that S1P is one of the key molecules to overcome the resistance to the drug therapies, such as hormonal therapy, anti-HER2 therapy, or chemotherapy, all of which are crucial aspects of a breast cancer treatment

Lymphangiogenesis: A new player in cancer progression

Lymph node metastasis is the hallmark of colon cancer progression, and is considered one of the most important prognostic factors. Recently, there has been growing evidence that tumor lymphangiogenesis (formation of new lymphatic vessels) plays an important role in this process. Here, we review the latest findings of the role of lymphangiogenesis in colorectal cancer progression, and discuss its clinical application as a biomarker and target for new therapy. Understanding the molecular pathways that regulate lymphangiogenesis is mandatory to pave the way for the development of new therapies for cancer. In the future, tailored treatments consisting of combinations of chemotherapy, other targeted therapies, and anti-lymphangiogenesis agents will hopefully improve patient outcomes. This progression to the clinic must be guided by new avenues of research, such as the identification of biomarkers that predict response to treatment