Breast Cancer Management最新文献

Screening mammography is recognized as an imperfect imaging tool that performs poorly in women with dense breast tissue - a limitation which has driven demand for supplemental screening techniques. One potential supplemental technique is molecular breast imaging (MBI). Significant improvements in gamma camera technology allow MBI to be performed at low radiation doses, comparable with those of tomosynthesis and mammography. A recent screening trial in women with dense breast tissue yielded a cancer detection rate of 3.2 per 1000 for mammography alone and 12.0 per 1000 for the combination of mammography and MBI. MBI also demonstrated a lower recall rate than that of mammography. MBI is a promising supplemental screening technique in women with dense breast tissue.

Helping patients to maximize their autonomy in breast cancer decision-making is an important aspect of patient-centered care. Shared decision-making is a strategy that aims to maximize patient autonomy by integrating the values and preferences of the patient with the biomedical expertise of the physician. Application of this approach in breast cancer decision-making has not been uniform across cancer-specific interventions (e.g., surgery, chemotherapy), and in some circumstances may present challenges to evidence-based care delivery. Increasingly precise estimates of individual patients' risk of recurrence and commensurate predicted benefit from certain therapies hold significant promise in helping patients exercise autonomous decision-making for their breast cancer care, yet will also likely complicate decision-making for certain subgroups of patients.

Breast density is one of the strongest predictors of breast cancer risk. Women with the densest breasts are 4 to 6 times more likely to develop cancer compared with those with the lowest densities. Breast density is generally assessed using mammographic imaging; however, this approach has limitations. Magnetic resonance imaging and ultrasound tomography are some alternative imaging modalities that can aid mammography in patient screening and the measurement of breast density. As breast density becomes more commonly discussed, knowledge of the advantages and limitations of breast density as a marker of risk will become more critical. This review article discusses the relationship between breast density and breast cancer risk, lists the benefits and drawbacks of using multiple different imaging modalities to measure density and briefly discusses how breast density will be applied to aid in breast cancer prevention and treatment.

Metastasis is a complex phenotype that is not discrete, is polygenic, varies in range over the entire population and follows non-Mendelian inheritance. Recent evidence indicates that inherited susceptibility affects not only the development of the primary tumor, but is also an important factor in progression and metastasis. Since metastasis accounts for the majority of breast cancer deaths, identification and understanding of the genetic modifiers of metastasis underlies success of personalized therapy. Studies from our laboratory and others have now characterized several metastasis susceptibility factors. While an important step forward, these certainly do not describe the entire metastatic phenomenon and efforts continue to expand this knowledge. Here we review the complex metastatic process and current knowledge on the genetics of breast cancer metastasis, including germline polymorphisms that have been associated with the disease.

Despite the tremendous efficacy of trastuzumab against HER2-overexpressing metastatic breast cancers, a significant fraction of women demonstrate progressive disease during treatment. Multiple mechanisms have been proposed to mediate trastuzumab resistance. In this mini-review, we discuss the evidence supporting FOXM1 as a mediator of resistance and potential new therapeutic target in trastuzumab-refractory breast cancer. FOXM1 expression is significantly elevated in multiple breast cancer data sets. Some studies suggest a direct correlation between FOXM1 and HER2 expression levels. In addition, overexpression of FOXM1 reduces the sensitivity of HER2-positive breast cancer cells to trastuzumab or lapatinib. Conversely, knockdown or pharmacological inhibition of FOXM1 rescues resistance to HER2-targeted therapies. Current pre-clinical information supports further investigation of the role of FOXM1 in trastuzumab-resistant breast cancer.

Transforming growth factor (TGF-β) is a multifunctional cytokine that plays essential roles in regulating mammary gland development, morphogenesis, differentiation, and involution. TGF-β also regulates mammary gland homeostasis and prevents its transformation by prohibiting dysregulated cell cycle progression, and by inducing apoptosis; it also creates cell microenvironments that readily inhibit cell migration, invasion, and metastasis. Interestingly, while early-stage mammary tumors remain sensitive to the tumor suppressing activities of TGF-β, late-stage breast cancers become insensitive to the anticancer functions of this cytokine and instead rely upon TGF-β to drive disease and metastatic progression. This switch in TGF-β function is known as the "TGF-β Paradox" and represents the rationale for developing chemotherapies to inactivate the TGF-β pathway and its oncogenic functions in late-stage breast cancers. Here we outline the molecular mechanisms that manifest the "TGF-β Paradox" and discuss the challenges associated with the development and use of anti-TGF-β agents to treat breast cancer patients.

Pregnancy and its effects on breast cancer risk have been widely investigated; there is consensus among researchers that early pregnancy confers protection against breast cancer later in life, whereas nulliparity and late-age parity have been associated with increased risk of developing breast cancer. The answer to the question of how pregnancy reduces breast cancer risk has been elusive; however, pregnancy, like breast cancer, is a similar hormone-dependent entity under direct control of estrogen, progesterone and, of particular importance, human chorionic gonadotropin (hCG). In this report, we emphasize the main changes, previously described by our laboratory, in morphology and gene expression levels of the mammary gland of Sprague-Dawley rats exposed to known cancer-preventative conditions (pregnancy, hCG and progesterone + estrogen). In addition, we postulate a protective mechanism induced by hCG that could reduce the cell's potential to be transformed by carcinogens.