Combined Treatment Of Locally Advanced Breast Cancer

Breast cancer is one of the common malignant tumors among women. Every year in the world, about 1.2 million women suffer from breast cancer and 500,000 people die of it. The incidence of breast cancer comes first among female malignant tumors in developed countries in West Europe and North America. In recent years, the incidence of breast cancer in our country is increasing year after year and it differs greatly from that in western countries: l.peak incidence is among 40-49-year-old women, 10-15 years earlier than that of western women. 2. patients go to see a doctor at relatively advanced stages. In accordance with the characteristics of breast cancer in our country, domestic medical community has made considerable progress in treatment of breast cancer after years of deep-going researches. Before, many LABC cases were considered inoperable or operated with unsatisfactory results. After Combined treatment, recurrence and metastasis have been obviously reduced and survival rate greatly increased.Up to now there is no clear definition of locally advanced breast cancer (LABC). It is usually regarded as III stage breast cancer, with mecrometastatic but no distant metastasis and hard to be removed by surgery. It includes: 1. locally recurrent breast cancer. 2. IIIA stage breast cancer, with homolateral lymphatic metastasis, mutually confluent and fixed with other tissues, tumor larger than 5 cm accompanied by axillary lymph nodes metastasis, but not fixed. 3. MB stage breast cancer, any tumorinvading chest wall or skin, with axillary and intrabreast lymph nodes metastasis or any tumor with intrabreast lymph nodes metastasis. 4. inflammatory breast caner 5. supraclavicular lymph nodes metastasis in affected side without distant metastasis in other organs. Combined treatment of LABC includes:1. Surgery: It is one of the main treatments of breast cancer. Radical operation of mastocarcinoma, initiated by Halsted, has been followed in the past hundred years, LABC should be removed as completely as possible.. Radical operation of mastocarcinoma mainly applies to cases of IIIA and IIIB breast cancer, LABC cases receiving preoperative chemotherapy or partly relieved by radiotherapy. Modified radical mastectomy mainly applies to cases of IIIA and IIIB breast cancer receiving preoperative chemotherapy or cases of decreased stage after having radiotherapy. Simple mastectomy mainly applies to old and weak patients with functional damage in important organs like heart or lungs and cannot accept Radical operation of mastocarcinoma or Improved radical mastectomy, LABC, relief of tumor for cases of advanced breast cancer before radiotherapy or chemotherapy. Skin grafting should be performed if necessary.2. Chemotherapy: It is one of the main treatments of infiltrating breast cancer. Through chemotherapy, survival rate could be greatly increased and survival quality much improved. It includes preoperative neoadjuvant chemotherapy and postoperative chemotherapy. Since 1970s, "sandwich" treatment — neoadjuvant chemotherapy — local treatment (operation or plus radiotherapy) ~ postoperative chemotherapy has been applied to cases with difficulty in surgical resection and satisfactory results have been achieved. With neoadjuvant chemotherapy, the tumor would obviously shrink until it disappears and changes in tumor after chemotherapy could be directly observed. Thus, reliable evidences could be provided for clinical chemotherapy plans. Reaction of primary tumor and changes in axillary lymph nodes after the neoadjuvant chemotherapy are chief prognostic factors influencing total survival rate and anosis survival rate. After chemotherapy, primary tumor will disappear, survival rate of cases of complete pathological disappearance or negative lymph node increase obviously.At present, the focus of the neoadjuvant chemotherapy is on improving the reaction of tumors to chemotherapy. In order to find effective chemotherapautic medicine, it has been reported in recent years that some biological factors such as cerb-B2, P53, Ki-67, cell apoptosis index and Bcl-2 have been used as quota predicting drug sensitivity. It is believed that with the development of the research and exploration of more effective chemotherapy plans, neoadjuvant chemotherapy will be applied more reasonably and breast cancer will be treated more effectively. Common postoperative chemotherapy includes: CMF and CAF or AC. Current research indicates that CAF or AC is better than CMF. The application of Taxol in mid 1990s is an important breakthrough in breast cancer chemotherapy. Taxol and Anthracycline drugs are the principal and the most effective chemotherapy medicine in clinical treatment of breast cancer, and combined chemotherapy is better than chemotherapy with single medicine. Researches in recent years indicate that for cases of advanced breast cancer, chemotherapy with Gemcitabine combined Taxol is obviously more effective than that with Taxol only.3. Electrochemotherapy (EchT): EchT is a kind of therapy, through which a series of electrochemical reactions occur so that the microcirculation of the tumor tissue will change and the tumor cell will degenerate, denaturalize and die under the action of direct current and pulse current, thus the tumor will be treated. In recent years, this therapy has already been used to treat LABC, including those suffer from skin diabrosis because of the invasion of primary tumor and those suffer from recurrence of thoracic fold. The curative effect of the method is remarkable, which is equal to that of non surgical removal of the tumor without bleeding, especially to those of advanced breast cancer who are suffering the pain, bleeding and cacosmia caused by the tissue necrosis. EchT is an effective way of treat advanced breast cancer with more normal tissue remained and little body function influenced.4. Radiotherapy: Radiotherapy is one of ways of treating LABC whose therapeutic effect is rather limited which cannot kill all the tumor because of the influence of the biological effect of the rays, which is often used in Combined treatment currently. The former radiotherapy used to be palliative, but with thedevelopment and improvement of radiotechnology and radiobiology, locally tumor can receive high dose without hurting the normal tissue around, and thus a good locally therapeutic effect can be achieved.5. Endocrinotherapy: It is very clear that estrogen is the key irritant to induce breast cancer. The growing of the cancer cell can be checked and the remedial effect can be improved through the therapy in which the hormone's mediation into the growth and differentiation of the cell is removed, restrained, interdicted and interfered. Endocrinotherapy is now playing a more and more important role in the chemical prevention and the Combined treatment with the molecular basis becoming clearer and clearer and with the exploiture of new type endocrine drugs. In recent years, in addition to the widely used front line anti-estrogen drugs with Tamoxifen as their representative, a new generation aromatizing enzyme inhibitor, such as Letrozole, Femara are used extensively as second line drugs to treat ambulant mammary cancer after menopause. For ER positive ambulant breast cancer before menopause, different therapeutic methods can be used, including surgical removal and GnRH of the kind drugs such as Goeserelin(Zoladex).6. Biotherapy: With the march of molecule biology, cell biology and immunology, biotherapy including immunotherapy and genotherapy, whose theory is regulate the biological reaction of the mechanism itself so as to curb or kill the tumor through the defensive reaction of the tumor host or the effect of biologicals, has become a very promising therapeutic means following surgical therapy, chemotherapy, endocrinotherapy.The immunotherapy of LABC is a rather new field, including specific therapy, such as monoclone antibody, tumor bacterin and nonspecific immunoregulation therapy, such as cell genes, T-cell therapy. The strategies of tumor bacterin are tumor genetic engineering bacterin, peptid bacterin and nucleic acid bacterin. The cell genes and immunocompetence cells treating breast cancer mainly include IFN, IL-2, TNF, CSF, LAK, DC and CTL, which are frequently combined with other biotherapy and chemotherapy. Recently, the implication of Herceptin, which is the first biological gene targeted curative in history, is a breakthrough in the antibodytherapy of breast cancer. Herceptin, which can be conbined with cerbB-2 receptor on the cell surface thus to check the growing of the breast cancer cells and to create the cell mediated and dependent cell-mediated cytotoxicity, is monoclone antibody against HER-2 derived from the recombination of DNA. This method can help those with over expression of HER gene with the rising of tumor laxation rate and the prolonging of survival time.The theory of genotherapy is to achieve the therapeutic purpose through transmiting the intent gene into the target cells by means of gene transferring technology, with the intent gene acquiring specific function by expressing the target gene to achieve or mediate the effect of curbing and killing the tumor. The main methods are suicide gene therapy, tumor-restraining gene therapy, wither-relative gene therapy, anti-vessel-formation gene therapy and combined therapy of various genes. Currently genotherapy falls into the phase of experimental study, but the results are very encouraging so that it is predicted that a breakthrough will be achieved in a few years.In sum, by means of the Combined therapies mentioned above in treating LABC, we are able to control the locally recurrence rate, increase the survival rate and improve the life quality of the patients.