The 4th large meta-analysis of all trials of the treatment of operable breast cancer: increased survival after a longer follow-up

The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) was founded in 1983. The EBCTCG coordinates the quinquennial worldwide meta-analyses of centrally located data on women in all randomised trials of early breast cancer. This 4th meta-analysis, with a follow-up of 15 years, showed an increased survival after the use of adjuvant hormonal or chemotherapy. The EBCTCG analyses have been responsible for major changes in the treatment of breast cancer in the past. However, we do not need another meta-analysis before implementing, for example, the improvement of chemotherapy with taxoids and the improvement of hormonal treatment with aromatase inhibitors. Nowadays, new treatments are implemented before the 5-year follow-up and are aimed more specifically at certain tumour characteristics.     

Tamoxifen therapy in breast cancer control worldwide.

In most developed and many developing countries, breast cancer is the most frequent cancer and the leading cause of cancer death among women. At least 50% of all breast cancer patients worldwide would survive longer, however, if public awareness about and early detection of the condition were increased and greater use were made of efficient treatment of proven value. With early-stage, localized breast cancer, local treatment combined with adjuvant hormonal therapy with tamoxifen, a synthetic estrogen, could save the lives of 6 women out of 100 compared with local treatment alone. Tamoxifen has anti-estrogenic effects not only on breast cancer cells but also on liver metabolism and bone, with concomitant decreases in risk factors for chronic skeletal and vascular system diseases. Long-term tamoxifen treatment causes major adverse clinical effects in < 5% of women; menopausal and vasomotor symptoms occur in the majority of treated women, but their severity lessens over time. Tamoxifen is being considered as a standard therapy and is included in the WHO list of essential drugs for the treatment of breast cancer patients in both developing and developed countries. For the control of breast cancer more successfully worldwide, one challenge is to make tamoxifen therapy available to greater numbers of women.     

Breast cancer in patients, 70 years or older

Over 30% of breast cancers are diagnosed after age 70. The incidence of breast cancer in the elderly has increased since 1960. Risk factors for breast cancer are a medical history without pregnancy, a first pregnancy after age 30 and the use of hormonal replacement therapy. The biology of breast cancer at advanced age indicates a relative slow, less aggressive and hormone dependent tumour growth. In spite of these favourable characteristics, the prognosis is not better than at middle age. Over 20% of older patients die from co-existing other diseases within 5 years after the diagnosis of breast cancer. This comorbidity, mostly cardiovascular or pulmonary, affects the possibilities and the outcome of treatment. Treatment of the primary tumour is performed according to the same guidelines as in younger patients. Indication exists for hormonal adjuvant treatment with tamoxifen in patients with oestrogen receptor positive tumours. Hormonal treatment is the treatment of choice in metastatic disease. Chemotherapy is given in patients with oestrogen receptor negative tumours and in patients with progressive hepatic or pulmonary metastases.     

宫颈癌的化疗

宫颈癌的主要治疗方案是手术和放疗,近年由于对宫颈癌综合治疗方案的广泛应用,特别是手术技术的改进,保留生育手术的兴起,使宫颈癌化疗逐渐受到重视。宫颈癌的化疗包括同步放化疗、术前新辅助化疗、术后辅助化疗及姑息化疗。新辅助化疗虽然在临床中应用广泛,但其疗效迄今仍尚未确定,而同步放化疗却得到了临床的进一步肯定。宫颈癌姑息治疗中的化疗,不能改善患者的远期生存质量。因此,化疗仍然是宫颈癌治疗的辅助手段。     

Screening for breast cancer

Breast cancer is a multifactorial disease that has a worldwide annual incidence of over 1 million cases. In the UK this equates to over 39000 new diagnoses per year. Most of these cases occur in postmenopausal women, and the incidence in both this age group and in younger women is rising. Most of the major risk factors for breast cancer such as female sex, age and a family history of the disease cannot be avoided. However, there is established evidence that earlier detection of breast cancer through mammographic screening does significantly reduce mortality, by up to 24%. Since its inception in 1989, the National Health Service Breast Screening Programme (NHSBSP) has become increasingly effective at detecting breast cancer in the target population of women aged over 50, and together with advances in surgery, chemotherapy and other adjuvant medical treatments, mortality from breast cancer is significantly decreasing. This contribution aims to explore the principles behind the NHSBSP, and will review the key evidence which supports it. The advantages and pitfalls of screening will be examined and an overview of the actual screening and assessment process is included. Screening in high-risk groups is a new and controversial area that is now gaining prominence, and new imaging techniques being used in such groups, in addition to the screening and assessment of breast cancers in the conventional age range, will be covered.     

Three men with breast cancer

In three men, aged 81, 66 and 58 years, breast cancer was diagnosed. All three were treated by modified radical mastectomy and axillary-node dissection. They received tamoxifen and the first and the third patient also received radiotherapy. Presentation of these patients is usually delayed, because of the rarity of and unfamiliarity with the disease. Consequently, the disease is often in a more advanced stage at presentation and overall mortality is higher in comparison with women with breast cancer. However, survival of male patients is similar to survival of female patients when matched for age and stage. This stresses the importance of a timely diagnosis. As in women, of the known risk factors for male breast cancer, a positive family history is one of the most important ones. Modified radical mastectomy, combined with sentinel-node biopsy by experienced teams, is the standard treatment. Criteria for adjuvant systemic treatment are identical for men and women, although hormonal therapy (tamoxifen) has a more prominent place in the adjuvant setting because of the high percentage of positive hormone receptors in men.     

Changes in endocrine therapy: anastrozole and advanced breast cancer in postmenopausal women

Emerging data on endocrine therapies necessitates a re-evaluation of treatment strategies for advanced breast cancer. In this review, we present data from recent studies of the third-generation, nonsteroidal aromatase inhibitor (AI) anastrozole that illustrate its changing role in the treatment of postmenopausal women with advanced breast cancer. These studies demonstrate that anastrozole is now a treatment of choice as first-line therapy for patients presenting with advanced breast cancer and for patients who have progressed to advanced disease after adjuvant therapy with tamoxifen. A further trial has also shown that anastrozole is an effective and well-tolerated alternative to tamoxifen as adjuvant treatment for postmenopausal women with early breast cancer.     

Racial and ethnic differences in adjuvant hormonal therapy use

Abstract Background: In the United States, 5-year breast cancer survival is highest among Asian American women, followed by non-Hispanic white, Hispanic, and African American women. Breast cancer treatment disparities may play a role. We examined racial/ethnic differences in adjuvant hormonal therapy use among women aged 18-64 years, diagnosed with hormone receptor-positive breast cancer, using data collected by the Northern California Breast Cancer Family Registry (NC-BCFR), and explored changes in use over time. Methods: Odds ratios (OR) comparing self-reported ever-use by race/ethnicity (African American, Hispanic, non-Hispanic white vs. Asian American) were estimated using multivariable adjusted logistic regression. Analyses were stratified by recruitment phase (phase I, diagnosed January 1995-September 1998, phase II, diagnosed October 1998-April 2003) and genetic susceptibility, as cases with increased genetic susceptibility were oversampled. Results: Among 1385 women (731 phase I, 654 phase II), no significant racial/ethnic differences in use were observed among phase I or phase II cases. However, among phase I cases with no susceptibility indicators, African American and non-Hispanic white women were less likely than Asian American women to use hormonal therapy (OR 0.20, 95% confidence interval [CI]0.06-0.60; OR 0.40, CI 0.17-0.94, respectively). No racial/ethnic differences in use were observed among women with 1+ susceptibility indicators from either recruitment phase. Conclusions: Racial/ethnic differences in adjuvant hormonal therapy use were limited to earlier diagnosis years (phase I) and were attenuated over time. Findings should be confirmed in other populations but indicate that in this population, treatment disparities between African American and Asian American women narrowed over time as adjuvant hormonal treatments became more commonly prescribed.     

Impact of the new guidelines for adjuvant systemic treatment of breast cancer at hospital level

Recently, the Dutch Society for Medical Oncology published new consensus guidelines for the use of adjuvant systemic treatment in patients with operable breast cancer. We used data of the cancer registry of the Comprehensive Cancer Centre South to predict the change in the number of patients who will be candidates for systemic treatment according to these new guidelines. It was estimated that of all patients with operable breast cancer, 15% should receive chemotherapy, 27% hormonal therapy and 17% a combination of both modalities. Of the patients with negative axillary lymph nodes, one-third will receive adjuvant systemic treatment. Compared with the previous guidelines, the introduction of the new guidelines will cause a 50% increase in the number of patients receiving adjuvant systemic treatment in Dutch hospitals.     

Management of Hormone-Responsive Postmenopausal Breast Cancer

Postmenopausal breast cancer is frequently hormone responsive and may be treated with agents that prevent estrogen activity. Tamoxifen is the most widely used of these agents, proving effective in both early and advanced disease. However, the role of tamoxifen has been challenged by the development of newer agents which have demonstrated at least equivalent activity and better tolerability, notably the nonsteroidal third-generation aromatase inhibitor anastrozole, which is currently the only other agent approved for primary adjuvant treatment of early disease and first-line treatment of advanced disease.In postmenopausal women with early breast cancer, anastrozole was associated with a significantly higher rate of disease-free survival (86.9% vs 84.5%) and a lower incidence of contralateral breast cancer than tamoxifen. Furthermore, the incidences of thromboembolic events and endometrial cancer were significantly lower with anastrozole. However, anastrozole was associated with an increase in musculoskeletal events (including fractures) and further evaluation of the clinical significance of this finding is warranted. Pharmacoeconomic analyses based on the results of this trial and conducted from different healthcare perspectives have all found anastrozole to be a cost-effective adjuvant therapy for early postmenopausal breast cancer. Clinical trial data indicate that switching patients who have already received 2 years’ tamoxifen treatment to anastrozole reduces the risk of relapse and death compared with continuing treatment with tamoxifen. Further studies are warranted to determine the optimum sequence of agents and duration of adjuvant therapy.Large well designed trials have also shown first-line anastrozole therapy is at least as effective as tamoxifen in prolonging time to disease progression and overall survival in patients with advanced disease. Current data indicate that the drug is more effective than tamoxifen in patients whose tumors are known to express the estrogen receptor. Pharmacoeconomic analyses conducted from various healthcare perspectives support the use of anastrozole as a cost-effective treatment in this indication.Anastrozole has demonstrated similar efficacy to that of other approved agents, including letrozole and fulvestrant, as second-line therapy for patients who have failed first-line therapy (in most cases with tamoxifen).In conclusion, clinical and pharmacoeconomic data support the role of anastrozole as a primary adjuvant treatment for use across the entire spectrum of breast cancer encompassing early disease through to advanced metastatic disease, and reflect current treatment guidelines. Anastrozole has also proven effective in clinical trials in the neoadjuvant setting, though its use in this setting and in breast cancer prevention remains to be fully elucidated.     

Dutch Institute for Healthcare Improvement guideline, "Treatment of breast carcinoma": important document but an open attitude to new "evidence" is necessary

In addition to the many international guidelines on the treatment of breast cancer, the Dutch Institute for Healthcare Improvement [Dutch acronym: CBO] has issued a Dutch national guideline on this subject, aided by representatives from the various medical professions involved and the patient advocacy group. A potential problem in reaching consensus on a practice guideline is the masking of controversies, which may hamper participation in new and innovative studies. Examples are the manner in which local and systemic treatments are combined and the consequences of new diagnostic modalities, for example the histopathologic presence of micrometastases in the sentinel node. The abridged version of the guideline published in this issue of the journal, scarcely allows space for specific problems such as the very young or old, pregnancy, hormonal substitution, male breast cancer and the patient with hereditary breast cancer. The authors of this guideline propose a nationwide registration of all patients plus follow-up to monitor the adherence to the guideline. The best way to study the quality of care and compliance with guidelines is still being debated in the medical literature. The money required for a nationwide registration of data on all patients including follow-up, might be better spent on measuring a number of indicators in a limited group of patients on the one hand and on devising new (randomised) trials on the other. This would result in the collection of better evidence for the many unanswered questions in the treatment of this common malignancy.     

Cancer and contraception: Release date May 2012 SFP Guideline #20121

As a result of advances in cancer diagnosis and treatment, young women within the reproductive-aged group are now more likely to survive cancer. Reproductive-aged women with cancer may be interested in deferring pregnancy either temporarily or permanently at cancer diagnosis, during therapy or after treatment. Currently, there are limited guidelines to aide clinicians in managing the contraceptive needs in this special population. After reviewing the evidence regarding the safety and efficacy of available methods of contraception for women who have been diagnosed with cancer, the Society of Family Planning recommends that women of childbearing age who are being treated for cancer avoid combined hormonal contraceptive methods (containing estrogen and progestin) when possible because they may further increase the risk of venous thromboembolism (VTE) (Level A). The copper T380A intrauterine device, a highly effective, reversible, long-acting, hormone-free method, should be considered the first-line contraceptive option for women with a history of breast cancer (Level A), although for women being treated with tamoxifen, the levonorgestrel-containing intrauterine system (IUS) which decreases endometrial proliferation may be preferable (Level B). Women who develop anemia may benefit from use of a progestin-containing contraceptive (Level A). Women who develop osteopenia or osteoporosis following chemotherapy should avoid the progestin-only contraceptive injection (Level B). More information is needed in many areas. There are insufficient data to evaluate the risk of VTE when progestin-only contraceptives are used by women at high risk of VTE. Information is also needed on whether the levonorgestrel-containing IUS affects the risk of breast cancer recurrence and whether hormonal contraceptives affect the risk of breast cancer among women who have received chest wall, or "mantle field," radiation. Finally, studies of the safety and effectiveness of IUS use by women who are immunosuppressed and studies of whether progestin-only contraceptives affect the risk of fracture among cancer survivors or, more generally, women with osteopenia would be useful.     

Effective treatment strategy in elderly breast cancer patients

INTRODUCTION: High frequency of cancer in older people and the improvements in life expectancy do not allow older age to be a barrier to treatment. The age is one of the risk factors for breast cancer development, one third of all cases occur in women older than 70 years. AIM: To provide an overview of the available information on the main issues in the field of surgery, radiotherapy and medical approaches to the treatment of breast cancer in the elderly. METHOD: The author discusses the treatment of breast cancer in the elderly, based on the data of literature. RESULTS: The assessment of any patient is the first step in the treatment process, performance status is more important than age. In older women a correct evaluation includes not only the basic medical history and the cancer staging, but also a detailed assessment of health and environment that may interfere with the therapeutic approach of the patient. Age is not a limitation for surgery, without any comorbidity it is safe, and operative mortality is low. The body self-image is important for most old women, they also wish to keep their breasts, so a conservative surgery and adjuvant radiotherapy should be offered to all, as long as the stage permits it. The selection of patients who are candidates for axillary dissection is based on selective lymph sentinel node technique which provides an optimal nodal staging with a minimal morbidity. The results of radiotherapy are as good as in younger patients, elderly women tolerate radiotherapy well. The inability to travel to the radiation facility is often the reason for omitting the radiation treatment and to choose a modified mastectomy. A promising alternative to the standard radiation treatment is the concept of intraoperative radiotherapy. Breast cancer in the elderly women is more likely to be well differentiated tumour, containing oestrogen and progesterone receptors. Based on these favourable prognostic factors, endocrine therapy is the standard treatment in adjuvant and metastatic setting for older women. When all hormonal options have been exhausted, elderly women should be treated with chemotherapy. Older patients often use several drugs concomitantly, and this polypharmacy may lead to possible clinically significant changes in the cytotoxic agent pharmacology. Supportive care can improve compliance of patients to chemotherapy. The introduction of oral and weekly applied cytotoxic treatments will allow a broader spectrum of patients to benefit from chemotherapy, particularly those with a poorer performance status. CONCLUSIONS: The use of a multidimensional geriatric evaluation permits a better selection of the best and individualized therapeutic decision for each patient. The growing number of treatment options in the elderly breast cancer patients will lead to an increase in survival and contribute to an improvement in their quality of life.     

High dose chemotherapy for breast cancer: the case for trials in adjuvant therapy.

Adjuvant polychemotherapy reduces the annual mortality for breast cancer, the effect being seen for at least the first decade after primary treatment for stage II disease. However, the overall benefit is modest with an annual reduction in the odds of death of the order of 20%-30%. For patients at standard or low risk of recurrence this appears to be an acceptable benefit given low toxicity of treatment. However, some patients have a very much worse prognosis identifiable on the basis of the number of involved axillary nodes at surgery. Patients with more than 10 lymph nodes, for example, have a predicted survival of less than 30% at 5 years and around 10% at 10 years. High dose chemotherapy has shown immediate benefits in terms of complete response rates in advanced breast cancer. Potential benefits of this treatment could be even higher in the adjuvant setting given the patient's fitness and the fact that micrometastatic disease represents the best clinical analogue of the successful laboratory experimental conditions. Now that the safety factors appear to be favourable with a treatment-related mortality of less than 5% it would appear that stage II poor risk disease is an appropriate setting to test high dose chemotherapy against the best conventional therapy in randomized trials.     

The sentinel lymph node procedure also feasible in patients with recurrent breast cancer

The sentinel lymph node (SLN) concept has become a standard option for the diagnosis and treatment of patients with primary invasive breast cancer. The implementation of this SLN concept has created a new category of patients: those who had breast-conserving therapy without complete axillary lymph node dissection following a negative SLN biopsy. In cases of local relapse in the ipsilateral breast, questions arise on the lymphatic drainage of this new tumour. Such is also the case for patients who have been treated for ductal carcinoma in situ, who have had a previous mastectomy, or even after previous benign breast or axillary surgery. To date the literature on SLN biopsy in patients with recurrent breast cancer is scarce: only to publications dealing with 116 patients. It is concluded that a SLN procedure in recurrent disease is feasible and can possibly lead to the identification of specific or aberrant lymphatic drainages. This could then lead to useful changes being made to the multidisciplinary treatment strategy in selected patients following a successful SLN biopsy. Since there are still no proper guidelines for performing such a repeat SLN biopsy, it is necessary to reach consensus on this new indication in the short-term.     

Breast cancer and protein biomarkers

Breast cancer is a healthcare concern of women worldwide. Despite procedures being available for diagnosis, prognosis and treatment of breast cancer, researchers are working intensively on the disease in order to improve the life quality of breast cancer patients. At present, there is no single treatment known to bring a definite cure for breast cancer. One of the possible solutions for combating breast cancer is through identification of reliable protein biomarkers that can be effectively used for early detection, prognosis and treatments of the cancer. Therefore, the task of identification of biomarkers for breast cancer has become the focus of many researchers worldwide.     

Comparison of adjuvant therapies using quality-of-life considerations.

The benefit for patients with operable breast cancer treated with adjuvant systemic therapy is small, if reduction of early mortality within the context of randomized control trials is used for treatment comparison. One might consider that the 75%-85% of patients who die despite treatment are overtreated, as are patients who remain alive even without therapy within a given time frame. Larger treatment benefits in terms of avoided or delayed breast cancer relapse have been demonstrated even at early phases of follow-up in the vast majority of adjuvant trials. Exposure of all patients to adjuvant therapy at a time at which no symptoms of disease are present is detrimental in terms of quality of life. Based on our assumption that the quality of life of the patient is typically altered both by subjective toxic effects of adjuvant treatment and by the appearance of relapse, we developed a method of comparing treatment effects in terms of time without symptoms of disease and toxicity of treatment (TWiST). Because the impact of treatment on relapse rates appears earlier than survival effects in all adjuvant therapy trials, and because the value of time without relapse in terms of the quality of life of the patients is as yet poorly defined, we have generalized our method of comparing treatment attitudes to include individual qualitative judgment values. The experience gained from integrating quality-of-life issues into clinical trials for breast cancer might also be applied to other diseases characterized by a chronic course, toxic treatments, and gains in periods of relative or absolute freedom from toxic effects and progressive disease.     

乳腺癌应用保乳术辅助放疗的临床疗效观察

目的 探究乳腺癌应用保乳术辅助放疗治疗的临床疗效观察。方法 资料随机选自2011年6月-2013年6月在本院诊治的乳腺癌患者62例,按照随机随机数字表方法将患者分为两组,每组31例,以保乳术辅助放疗患者作研究组,以改良式根治手术辅助化疗治疗作对照组,分析两组患者治疗后的美容效果、相关治疗指标、皮肤分级以及预后情况。结果 研究组乳房的美容效果优良率77.42%,对照组32.26%,两者比较具统计学意义(P < 0.05);且两组就出血量、手术时间情况,比较具有统计学意义(P < 0.05);同时两组放疗后皮肤反应各分级的例数,以及患者预后的局部复发率、远处的转移率、生存率情况比较,差异不具有统计学意义(P > 0.05)。结论 对于乳腺癌患者应用保乳术辅助放疗治疗,效果显著,具有一定临床研究和应用价值。