Twenty-five years after its first description the p53 protein has been shown to play a key role in both cancer and ageing. The p53 protein is activated by many different stress pathways, including oncogene action and DNA damage. The elucidation of the p53 response, which is aberrant in most cancers (including breast, lung, stomach and colorectal cancer), has provided many new targets for drug development and p53 gene therapy is now approved in China. In tumours where p53 is mutant small molecules may be able to restore its function. In many tumours the wild-type p53 gene remains intact but its function is compromised by loss of upstream signalling pathways or downstream effectors.A key regulator is Mdm2, an E3 ubiquitin ligase, that binds and ubiquitinates p53 and directs its degradation via the proteosome. Small potent peptides that can block the p53 Mdm2 interaction and activate the p53 response have been described. Growing selections of lead small molecules that mimic the action of these peptides have also been recently discovered. Cell-based screens have revealed that inhibitors of nuclear export and inhibitors of transcription (one of which is in clinical trial) can also activate the p53 response therapeutically. The pharmaceutical regulation of the p53 pathway offers great hope for improved treatment of human cancer. 2Mammographic screening with a breast cancer prevention programme Because of the heterogeneity of breast cancer from nodule to nodule, single findings cannot achieve the sensitivity or the negative predictive value necessary to identify a low-risk group that can be offered the option of follow-up (ACR Breast Imaging Reporting and Data System [BIRADS] 3 group). However, by using multiple findings in a strict algorithm, such a group can be identified. It is also important to keep in mind that breast cancer can be heterogeneous within an individual nodule. Part of the nodule may have circumscribed features that simulate a benign lesion, while another part may be spiculated and obviously malignant. Only by scanning the whole surface and substance of the nodule in two orthogonal planes (radial and anti-radial) can the presence of suspicious findings be excluded, and if there is a mixture of benign and suspicious findings, the benign findings should be ignored.These studies show that sonography is useful in the characterization of solid breast masses. Characterizing solid breast nodules into BIRADS categories defines carcinomas that might have been missed clinically or mammographically. It identifies a BIRADS 3 group that has far less than 2% risk of being malignant and can offer the patient the option of followup rather than biopsy. Currently, approximately 80% of patients with BIRADS 3 solid nodules are electing to be followed rather than to undergo biopsy. It improves the accuracy of the diagnosis of malignant breast lesions. Importantly, it also accurately defines a population of benign solid breast lesions that do not require biopsy when strict sonographic criteria of benignity are present.To a...
From 1930 to 1990 annual age-adjusted breast cancer death rates for women in the United States remained remarkably constant, oscillating around 32 deaths per 100,000 over 60 years. During this long timeframe, the surgical treatment of breast cancer evolved from radical mastectomy with mandatory lymph node dissection to lumpectomy coupled with radiation therapy. With this new paradigm, lymph node dissection was reserved for women with tumor-invaded axillary lymph nodes. Beginning in the 1970s, chemotherapy after surgery (adjuvant) and before surgery (neoadjuvant) was added to surgical treatment. The radical diminution in the scope of breast surgery did not alter the national breast cancer death rate. Doing less surgery was neither harmful nor beneficial to long-term survival from breast cancer. In the 1980s two events changed this static picture: the addition of tamoxifen to adjuvant and neoadjuvant chemotherapy, and the introduction of mammography. Beginning in 1990 annual breast cancer death rates in the United States began to fall, and have continued to fall each year since then. In 2001, the last year of published statistics, the breast cancer death rate was 26 deaths per 100,000. Best estimates for where to credit this dramatic drop in death rate place approximately 50% of the credit with improved adjuvant chemotherapy and 50% with mammography. Abnormal mammograms demand a breast biopsy since only one in five abnormal mammograms is actually a breast cancer. Consequently, widespread adoption of mammography has produced an image-guided breast biopsy industry in the United States. Open, surgical breast biopsy has been replaced with image-guided breast biopsy because improved breast biopsy tools have made image-guided breast biopsy equivalent in accuracy to open, surgical breast biopsy. These tools, in turn, have changed the professional lives of surgeons, pathologists, and mammographers, leading to the development of dedicated breast surgeons, breast pathologists, and interventional breast radiologists.
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