Breast cancer

Seasonal variation has been demonstrated in connection with several aspects of primary breast carcinoma. This report describes a seasonal variation in the growth of breast carcinoma in the axillary nodes that has not been reported previously and has prognostic implications. The nodes from a series of 301 node-positive breast cancer patients were investigated prospectively for the presence/absence of tumour cells in their efferent lymphatic vessels, the former being of poor prognosis. Their presence, i.e. positive EV-status, is common in nodes with established tumour growth. Many more patients coming to operation in the first 6 months of the year showed such findings, while more of negative EV-status were found in the second half (chi(2)=13, P<0.0005). Positive EV-status was, as expected, associated with poor prognosis relative to EV-negative (chi(2)=14). Its prognostic impact did not alter with season. It may be of note that seasonal variation in the arrival of micrometastases at the nodes has also been reported recently. These two phenomena may have a common pathogenesis.     

Breast cancer

In Japan, the incidence rate of breast cancer is increasing every year so as to become the most common cancer among Japanese women. One of every 16 women is anticipated to eventually suffer from breast cancer. However, unlike the incidence rate, the mortality rate of breast cancer is low, and the 5-year survival rate is about 80%. Mammography screening has been shown to be effective, but the screening rate is still low(20-30%), compared to screening rates for other organs. To increase the screening rate, the Japanese government has introduced free breast cancer screening. To make the system for breast cancer screening more efficient, we should determine the risk factors for Japanese women, and conduct such screening at public expense.     

Breast cancer

As most of the clinical evidence that has a significant impact on the care of breast cancer is based on studies conducted in Western countries, it is important to understand the differences in the natural history of the disease as well as in the patterns of care before applying that evidence to daily practice in Japan. For example, the EORTC 22881 study demonstrated significant improvement of local control after breast conserving therapy with the additional use of 16 Gy of boost irradiation to the tumor bed after 50 Gy of whole breast irradiation for margin negative patients. However, the extent of the surgery in this study was smaller than that common in Japan, and the criteria for a negative margin was less strict than that in Japan. Therefore, it may be over-treatment to give boost irradiation routinely to margin negative patients in Japan. On the other hand, as it is a universal observation that patients under the age of 40 have greater risk of local recurrence, the result of EORTC 22881 study that the benefit of boost irradiation was greatest in patients younger than age of 40 encourages us to confirm this finding in our own clinical settings. It is desirable to develop clinical evidence of high quality in Japan that are directly applicable to Japanese patients.     

Breast cancer

Several interesting aspects of breast cancer were covered at this year's American Society of Clinical Oncology meeting. Sentinel lymph node (SN) mapping is now in widespread use, in concert with the general trend toward trying to decrease the morbidity of breast cancer surgery. With every advance, however, comes new challenges, and there was a timely presentation from Giuliano's group addressing the controversial issue of how to interpret the presence of cells in the SN seen only with keratin stains but not by routine hematoxylin and eosin stains. Two abstracts addressed the issue of whether for certain women with invasive breast cancer radiation therapy could be omitted after lumpectomy. Another interesting topic related to hormonal issues in the adjuvant treatment of premenopausal women. An analysis from the ZIPP-TRIAL reported on bone marrow density studies in young women given two years of ovarian suppression in the adjuvant setting: it seems that the loss of bone density may be reversible and, more interestingly, may be prevented with concurrent tamoxifen. Two other presentations looked at the prognostic significance of drug-induced amenorrhea in young women treated with adjuvant chemotherapy and at the efficacy of ovarian suppression during chemotherapy in preserving fertility. In an unpublicized presentation, Mary-Claire King presented very interesting results from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial suggesting that tamoxifen may be an effective chemopreventive drug for women with BRCA2, but not BRCA1, mutations. Two important presentations re-analyzed the outcome of the pivotal trials using Herceptin to treat metastatic breast cancer and nicely show that FISH analysis of HER-2 overexpression is a more accurate indicator of response to Herceptin than immunohistochemical staining. Finally, there were two interesting presentations related to tamoxifen resistance which may be relevant clinically, pertaining to subsequent raloxifene use and the interaction of the estrogen receptor and EGF receptor pathways, respectively.     

Breast cancer

If generalizations can be drawn from these two sessions, we would suggest that evidence can be seen in support of certain principles for the chemotherapy of breast cancer. These principles are: Combination chemotherapy. Doxorubicin-containing combinations are superior to others in terms of improved remission rates. In the past decade, combination chemotherapy has resulted in significant improvement of survival in patients with disseminated breast cancer, and with this approach a small fraction of patients with metastatic disease have remained in extended complete remission. Dose of drugs. Drug combinations utilized at lower doses result in lower response rates. Drug dose rate. When chemotherapy is interrupted for treatment of local disease in inflammatory carcinoma of the breast, the survival rate of patients is lower compared to the subgroups of patients where there is no interruption in the treatment.     

Breast cancer

Many studies have suggested that older women with breast cancer have tumors with less aggressive biological features such as small tumor size, higher expression of steroid hormone receptor, and absence of expression of HER2. The 3 major treatments for breast cancer are surgery, drug therapy, and radiotherapy. The treatment of choice is determined by many factors, particularly the biological characteristics of the tumor and the risk of recurrence; the same factors are used to determine the treatment of choice in elderly patients. Surgery, endocrine therapy, and radiotherapy are relatively less invasive treatments. However, chemotherapy is a highly invasive treatment especially given its side effects. Because few women older than 70 years have been enrolled in randomized controlled trials, evidence-based treatment guidelines, particularly with regard to adjuvant chemotherapy, are lacking. A few older patients with breast cancers have high-risk features such as positive lymph nodes, absence of hormone receptors, and presence of HER2 expression. Chemotherapy is recommended for those older women for whom the risk of recurrence is higher. The important factors influencing the choice of treatment for breast cancer are the risk of recurrence and efficacy of treatment. Life expectancy, comorbidities, and organ function are also features that have to be considered when treating the elderly.     

Breast cancer

In Japan the mortality and incidence rates of breast cancer have been increasing. In 2000, the number of breast cancer deaths in female was 9,171. In 1996, the aged adjusted incidence rate of breast cancer was 38.9, top among all of female cancers and the estimated number of female breast cancer patients was 29,448 in Japan. Therefore, efficient breast cancer screening system is urgently needed. In April 2000, breast screening using biennial mammography in combination with clinical breast examination instead of annual clinical breast examination alone was introduced for women aged 50 and over in Japan. However, the compliance of screening using mammography was less than 1% in the fiscal 2000 year. On the other hand, the compliance of screening with clinical breast examination alone was 6.5% in same period. These compliances were significantly lower than that of about 65% in the USA. Given the importance of the control of quality in screening mammography, a central committee for the quality control of mammographic screening has been established in order to educate doctors and radiographers and to assess image apparatus in each facility. As of April 2002, 1,409 out of 1,978 doctors that participated in the training program had obtained either grade A (instructor level) or grade B (adequate level). G?tzche and Olsen reassessed previous meta-analyses of screening mammography and concluded that screening for breast cancer with mammography was unjustified. Subsequently, reviews by U. S. Preventive Services Task Forces and the WHO reconfirmed the effectiveness of screening mammography in reducing breast cancer mortality. These controversies show the importance of assessment of screening mammography effectiveness in Japan.     

Breast cancer

Endoscopic breast conserving surgery was developed originally in JAPAN. Minimally invasive technique improved cosmetic shape of breast conserving surgery by reducing the size of scar and changing the position of surgical wounds. In the present time, transaxillary endoscopic partial mastectomy by using special lifting systems, transaxillary total mastectomy by using Co 2 inflation, endoscopic partial mastectomy, by areola approach, and endoscopic axillary lymphnode dissection were performed as standerd procedure. The clinical results were showed that the efficacy of breast conserving operation were equal compared with normal procedure. As indication of breast conserving operation, patients with the tumor, that was within 3 cm, were selected, and the volume of resected specimen were also keep below 30% of total volume of breast as cosmetic indication for prevent metamorphosis of breast. In the case with metamorphosis after operation, some kind of reconstraction will be necessary. Minimally invasive breast surgery was improved cosmesis of breast surgery, and the patients with early breast cancer will take more benefits by using this technique.     

Breast cancer screening

Radiographic imaging of the breast began in the early years of the twentieth century. Continuous advances in film quality, energy sources, targets, grids, and filters have all contributed to superior image resolution. Federal quality standards now regulate screening mammography, and mass screening for breast cancer has become widely accepted in the United States. Wider application of screening has resulted in a dramatic apparent increase in incidence rates of breast cancer; a large proportion of this increase is in ductal carcinoma in situ. During the past 30 years, nine prospective, randomized trials to evaluate the ability of screening mammography to reduce mortality from breast cancer have been completed. These trials show a 30% reduction in mortality for women ages 50–69 years, but the benefit to women aged 40–49 years remains uncertain. This uncertainty is largely attributable to the lack of properly designed and conducted studies to evaluate screening efficacy in younger women. Although there is no biological reason to predict poor screening performance in the younger age groups, the sensitivity of screening mammography is lower in younger women. Additional data suggest that screening intervals longer than 12 months are ineffective in women younger than 50 years. With shorter screening intervals, the cost associated with screening mammography is comparable to other life-saving measures widely applied in the population. New breast imaging techniques hold promise for superior image quality, but they remain investigational as tools for mass screening. Until primary prevention of breast cancer is a reality, mass screening remains available to reduce mortality from breast cancer.     

Breast cancer chemotherapy

Chemotherapy can be an integral component of the adjuvant management strategy for women with early-stage breast cancer. Modern adjuvant strategies now comprises one or more chemotherapy agents, hormonal maneuvers, immunotherapy agents, or experimental agents. The use of adjuvant chemotherapy is generally based on estimates of an individual's risk of recurrence and the expected benefit of therapy. However, risk-benefit calculations have recently become increasingly sophisticated as a result of advances in genetic testing and molecular marker identification as well as ongoing refinements in chemotherapy strategies. In this article we will review the role of important prognostic and predictive factors and the rationale for adjuvant systemic therapy and modern chemotherapy regimens in the management of women with early-stage breast cancer.     

Breast cancer epidemiology

The various risk factors for breast cancer have been recognized for many years. A table lists these established breast cancer risk factors together with the approximate magnitude of the increase in risk associated with them. Breast cancer incidence rates increase with age throughout the life span in Western countries, although the rate of increase is greater up to age 50 years than after 50 years. Breast cancer is more common among women in upper rather than lower social classes, among women who never have been married, among women living in urban areas, among women living in the northern US than in the southern US, and among whites than blacks, at least among those over age 50. Women in North American and Northern European countries have the highest risk for breast cancer, women in Southern European and Latin American countries are at intermediate risk, and women in Africa and Asian countries have the lowest risk. Yet, rapid rates of increase in incident rates have been noted in recent years in many Asian, Central European, and some South American countries. The later the age at which a woman has her 1st full-term pregnancy, the higher her risk for breast cancer; the earlier the age at menarche and the later the age at menopause the higher the risk; and among women who have a premenopausal oophorectomy, the earlier the age at which this occurs the lower the risk. Among postmenopausal women, obesity is associated with an increase in risk. Lactation is negatively associated with subsequent breast cancer risk. Some current research is considering potential risk factors that have not been well studied in the past, including alcohol consumption, cigarette smoking, caffeine consumption, exposure to diethylstilbestrol (DES), emotional stress, exposure to electric power, and lack of physical activity. Other areas of current research reviewed here include radiation, mammographic parenchymal patterns, a high-fat diet, use of oral contraceptives (OCs), use of estrogen replacement therapy, and endogenous hormones. Cigarette smoking and caffeine consumption do not appear promising as potential etiologic agents. The studies of the DES-exposed women and of OC users suggest that the timing of exposure may be critical, since the possible effect of both these hormonal agents may be limited to specific time periods of rapid breast development. If such a critical period does not exist in postmenopausal women, then there may be little effect of hormones used at this time. Studies with long-term follow-up and that include long-term users are essential to studies of effects of hormones and other exposures.     

Breast cancer chemoprevention

According to the National Cancer Institute Surveillance Epidemiology and End Results Cancer Statistics Review, the incidence of invasive breast cancer in the USA is 124 women per 100,000 population. Women at increased risk for breast cancer have three major options to reduce their risk, specifically screening, chemoprevention and prophylactic surgery. In this article, we focus on chemoprevention. There are three chemoprevention agents available to reduce breast cancer risk: tamoxifen, raloxifene and exemestane. In this article, we summarize the major randomized clinical trials investigating the use of these agents in the chemoprevention setting. Randomized controlled trials have shown that these agents can reduce breast cancer incidence, but the potential risks of these agents and their impact on quality of life should also be carefully considered. Indeed, it is always important to keep in mind that chemoprevention targets asymptomatic women, and therefore the decision to embark on this strategy should never be taken lightly.     

Breast cancer grading

Histological sections of the primary tumour from 496 women with operable breast cancer have been examined for purposes of histological grading by two observers working independently. Each found a similar distribution of grade through the series, and a virtually identical influence of grade on prognosis. This close agreement occurred despite a 30% disagreement as to grade in individual cases. It is suggested therefore, that this technique while of relevance to analysis of groups of cases is of very limited reliability in individual patient prognosis.