Effects of chronic hepatitis C infection on the treatment of breast cancer patients

BackgroundAlthough hepatitis C (HCV) is the most common blood-borne infection in the United States, little information exists about treatment of breast cancer in the setting of chronic HCV.Patients and methodsThe databases of the University of Texas M.D. Anderson Cancer Center (MDACC) Tumor Registry, Department of Breast Medical Oncology, and Department of Laboratory Medicine were cross-referenced for patients with breast cancer, who were also identified as having HCV. Eligible patients had a diagnosis of invasive breast cancer, breast cancer treatment at MDACC, and a diagnosis of HCV.ResultsDuring chemotherapy, 25% of patients experienced elevations in aminotransferases and 44% of patients required dose reductions/delays in chemotherapy. More than 60% of the patients who received chemotherapy demonstrated a grade 2 or greater complication. However, 92% of patients were able to complete the number of cycles specified in the initial chemotherapy plan.ConclusionsAs the majority of these breast cancer patients completed the initial chemotherapy plan, this study indicates that breast cancer patients with HCV can be treated with cytotoxic therapy. Comparison with historical controls showed similar rates of hepatic toxicity in the presence (or absence) of HCV, indicating that incidence of transaminitis may not be significantly affected by HCV.     

Primary chemotherapy for early breast cancer

The use of primary chemotheraphy represents a novel approach being used with increasing frequency in the management of early breast cancer. Many studies now testify to the usefulness of this modality in increasing the frequency of breast conservation. The acceptance of high-risk breast cancer as a systemic, and therefore predominantly medical rather than a surgical, disease suggests, however, that its role is likely to be far more reaching. While some trials have so far suggested the possibility of a survival benefit for this approach, definitive conclusions are not yet possible and await the final mature results from several large randomized studies. Even if such studies do not show a large extra benefit for primary chemotheraphy over existing adjuvant treatment, the use of the primary tumour as an in vivo model of individual chemosensitivity and the identification of molecular markers as early predictors of response, suggest that this approach will become an integral part of the modern multidisciplinary management of early breast cancer.     

Changes in the surgical treatment of breast cancer

The principle in surgery for breast cancer is to clean out and remove en masse the primary lesion within the breast as well as the lymph nodes (metastases) in the vicinity. This fundamental approach to surgical intervention was established by Halsted and Meyer at the close of the nineteenth century. This has been termed typical mastectomy to this day and standard radical mastectomy has been the method used. Later, a more expanded type of radical surgery was performed on somewhat more advanced cases, but a less radical approach then came about. Since 1960, the excision of nodes in the cerebrum and cerebellum was not used for early cancer, and in some cases a more conservative approach in which only part of the breasts was removed resulted, as Europe and the United States were heavily toward reduced operations. Thus, it was considered that axillary expurgation was needed, but that excision of nodes in the cerebrum and cerebellum was not essential in every case. One approach is less aggressive, whether as to the expurgation or excision of the surrounding area of the breast; in certain cases, treatment may be combined with radiation and the surgery minimized. The above-mentioned operative procedure which leaves brain nodes intact has been called modified radical mastectomy. This is subdivided into the Auchincloss method, in which modes in the cerebellum are extirpated, and the Patey method, in which the cerebral nodes are preserved. In Japan this approach has been used for breast cancer in Stage I and Stage II, with surgery gradually becoming the mainstream. Conservative breast operation procedures such as tumor extirpation, partial breast removal or segmental resection are still rare in Japan but very common in Europe and the United States. Since remote metastases frequently occur through the circulation in breast cancer, in recent years it has generally been regarded as a whole-body disease and, in terms of the advance of the cancer in each case, the method of surgery is selected. There is a strong tendency to combine surgery with other methods (radiation, chemotherapy, hormonal therapy).     

Bisphosphonate treatment and radiotherapy in metastatic breast cancer

Patients with advanced breast cancer frequently develop metastasis to bone. Bone metastasis results in intractable pain and high risk of pathologic fractures due to osteolysis. The treatment of breast cancer patients with bone metastases requires a multidisciplinary approach. Radiotherapy is an established treatment for metastatic bone pain. It may be delivered either as a localized low dose treatment for localized bone pain or systemically for more widespread symptoms. Bisphosphonates have been shown to reduce morbidity and bone pain from bone metastases when given to patients with metastatic bone disease. In vivo studies indicate that early bisphosphonates administration in combination with radiotherapy improves remineralization and restabilization of osteolytic bone metastases in animal tumor models. This review focused on a brief discussion about biology of bone metastases, the effects of radiotherapy and bisphosphonate therapy, and possible mechanisms of combination therapy in metastatic breast cancer patients.     

Surgery for breast cancer -- from radical mastectomy to breast-conserving surgery

Treatment for breast cancer requires a multidisciplinary approach. The role of surgical treatment for breast cancer has changed over the past several decades, while the paradigm shift in the understanding of the natural history of breast cancer has gone from local disease theory to systemic disease theory. Under these circumstances, surgical procedure has become less aggressive and less invasive. Also, the introduction of primary systemic therapy for breast cancer could modify local treatment. On the other hand, the significance of local control on long-term survival has emerged from meta-analysis. We should understand surgical treatment as part of the multidisciplinary treatment. In this review, we introduce a change in surgical strategy for patients with breast cancer, and discuss the role of surgical treatment with in the recent multidisciplinary treatment.     

Advances in multidisciplinary treatment of rectal cancer

To summarize the advances in the multidisciplinary treatment of rectal cancer and to analyze the existing problems and development prospects. The full text database retrieval system of MEDLINE and the periodicals of CHKD were searched. The words ＂rectal cancer, diagnosis, surgery, chemotherapy, radiotherapy, targeted therapy, analysis＂ were used as key words for retrieval of literature concerning the values and clinical significance of rectal cancer multidisciplinary treatment from January, 2000 to December, 2007. Thirty papers were selected, of which 26 were used in analysis at last. Accurate preoperative staging of rectal cancer is a key factor in the multidisciplinary and comprehensive treatment of patients. A new therapy which is combined with radical operation can reduce the rate of local recurrence, prolong survival time, and particularly, promote the rate of sphincter preservation. Radical surgery combined with adjuvant therapy is still recognized as standard treatment modality for the patients with rectal cancer in stage Ⅱ-Ⅲ. Total removal of resectable metastases followed by prompt standard adjuvant therapy may extend survival time. The introduction of new chemical drugs, drugs of targeting therapy, and a regimen of combination therapy may improve outcomes in treatment for rectal cancer patients. A treatment standard for rectal cancer patients needs to be actively pursued. Compared with colon cancer patients, there has not been sufficient evidence to confirm that the total survival rate of rectal cancer patients after multidisciplinary and comprehensive treatments has been improved; therefore, it needs to be further studied.     

Cost-effective treatment options in first-line therapy for advanced breast cancer in Japan

Concern regarding the economic aspect of cancer care has been increasing in the face of mounting healthcare expenditure in Japan. The need, not only for effective, but also for efficient treatment options in breast cancer care have been recognized in a broader context. In clinical practice, treatment options in first-line therapy for advanced breast cancer have become similar to those in Western countries in the past 5 to 10 years in the context of so-called 'evidence-based medicine' employing clinical evidence; whereas evidence of cost-effectiveness has been less acknowledged. Limited economic evidence suggests that current Japanese practice in first-line hormonal therapy is cost-effective. However, the efficiency of other options, such as chemotherapy, remains unknown. The expanding use of an expensive molecular-targeting agent, trastuzumab, has great implications for a treatment algorithm for breast cancer as well as for cost-effectiveness of care. Trastuzumab, of which use in first-line therapy was not found to be cost-effective in Western countries, is expected to be used for a number of HER2-overexpressing primary breast cancers in Japan. The extension of indication of this single agent would increase national healthcare expenditure by 0.1%. The authors believe explicit discussion on value for money of new expensive drugs would be unavoidable, not only among health policy makers, but also leading breast cancer specialists in Japan in the near future.     

Intrinsic and extrinsic flaws of the nomogram predicting bone-only metastasis in women with early breast cancer: An external validation study

BackgroundThe recently developed MDACC nomogram purports to predict the risk of bone-only metastasis in women with early breast carcinoma based on five clinical and pathological characteristics. We set out to externally validate and assess its robustness using a tertiary breast cancer centre database.MethodsAll consecutive women treated for early breast cancer in our centre between January 1989 and December 2013 and who had all the nomogram variables documented were eligible for analysis.ResultsWe identified 1255 eligible women for external validation analysis. The median follow-up was 54 months (range: 1–312) and time to initial metastasis 20 months (range: 1–80). The correspondence between the actual bone-only metastasis and the nomogram predictions implied poor calibration of the nomogram in the validation cohort, be it in the whole cohort or when stratified by breast cancer subtype.ConclusionThis external validation study of the MDACC nomogram showed limitations in its generalizability to a new and independent European patient population.     

Pathogenesis,prevention, diagnosis and treatment of breast cancer

Breast cancer is the most common cancer affecting women worldwide. Prediction models stratify a woman’s risk for developing cancer and can guide screening recommendations based on the presence of known and quantifiable hormonal, environmental, personal, or genetic risk factors. Mammography remains the mainstay breast cancer screening and detection but magnetic resonance imaging and ultrasound have become useful diagnostic adjuncts in select patient populations. The management of breast cancer has seen much refinement with increased specialization and collaboration with multidisciplinary teams that include surgeons, oncologists, radiation oncologists, nurses, geneticist, reconstructive surgeons and patients. Evidence supports a less invasive surgical approach to the staging and management of the axilla in select patients. In the era of patient/tumor specific management, the advent of molecular and genomic profiling is a paradigm shift in the treatment of a biologically heterogenous disease.     

Patterns of treatment for early stage breast cancers at the M. D. Anderson Cancer Center from 1997 to 2004

BACKGROUND:

The objectives of this study were to examine the patterns of use for adjuvant therapy and the changes in surgical practice for patients with early stage breast cancer and to describe how recent large clinical trial results impacted the patterns of care at The University of Texas M. D. Anderson Cancer Center (MDACC).

METHODS:

The study included 5486 women who were diagnosed with stage I through IIIA breast cancer between 1997 and 2004 and received their treatment at MDACC. A chi‐square trend test and multivariate logistic regression model were used to assess changes in treatment patterns over time.

RESULTS:

Among lymph node‐positive patients, the use of anthracycline plus taxane chemotherapy increased from 17% in 1997 to 81% in 2004 (P < .001). Meanwhile, the use of anthracyclines without taxanes dropped from 76% to 20% (P < .001) between 1997 and 2000. For postmenopausal patients who received endocrine therapy, the use of tamoxifen was replaced increasingly by the use of aromatase inhibitors (from 100% on tamoxifen in 1997 to 14% in 2004; P < .001). The percentage of women who underwent initial sentinel lymph node biopsy increased significantly during the period from 1997 to 2004 (from 1.8% to 69.7%, respectively, among patients who underwent mastectomy; and from 18.1% to 87.1%, respectively, among patients who underwent breast‐conserving surgery; P < .001).

CONCLUSIONS:

The results from this study suggested that key findings from adjuvant therapy and surgical procedures from large clinical trials often prompt immediate changes in the patient care practices of research hospitals like MDACC. Cancer 2009. © 2009 American Cancer Society.     

Current status of therapy for breast cancer worldwide and in Japan

The results of clinical trials conducted in Europe and North America have been incorporated into treatment strategies for breast cancer in Japan. Despite the use of similar treatment regimens, why has mortality from breast cancer been increasing in Japan? Procedures for surgical treatment and sentinel lymph node biopsy in breast cancer do not differ between Japan and Western countries, but the strategies for radiotherapy differ slightly. Hormonal therapy is now selected on the basis of scientific evidence, and similar regimens are used in Japan and Western countries. As for postoperative adjuvant chemotherapy, an anthracycline plus cyclophosphamide and taxane-based regimens are standard treatments in Japan and Western countries. In 2009, however, the results of two large clinical studies designed to determine whether intravenous or oral treatment was superior for postoperative adjuvant chemotherapy were reported in Japan. Both studies showed that relapse-free survival and overall survival (OS) at 5 years after surgery were similar for a combination of cyclophosphamide, methotrexate, and 5-fluorouracil and for tegafur/uracil. Many chemotherapeutic agents that are used to treat recurrent or metastatic breast cancer have not yet been approved in Japan. As for molecular targeted therapy, some agents that target the human epidermal growth factor receptor family have been approved in Japan, whereas angiogenesis inhibitors have not. The results of many clinical trials have been incorporated into clinical practice in Japan, therefore, the outcomes of breast cancer therapy have surpassed those in other countries. Many pivotal clinical trials have been conducted outside Japan. Treatment regimens that have been developed on the basis of these studies might be suitable for the management of breast cancer in Western women, but not for Japanese women because of differences in genetic factors, physique, body mass index, pharmacokinetics, and drug metabolism. Such regimens should be modified on the basis of the characteristics of breast cancer in Japan to develop treatment that is optimally suited for Japanese women. In particular, local studies of pharmacokinetics, pharmacodynamics, and optimal dose levels and treatment intervals should be carefully performed. The establishment of treatment regimens optimally suited for Japanese patients with breast cancer could put the brakes on the trend towards increasing mortality from breast cancer in Japan.     

Breast cancer: multidisciplinary care and clinical outcomes

A multidisciplinary approach to the management of breast cancer is the standard of care in developed health systems. We performed a systematic review to assess the extent and quality of evidence on whether multidisciplinary care (MDC), or related aspects of care contribute to clinical outcomes in breast cancer, and in particular whether these influence survival. Only two primary studies have looked at MDC and neither of these studies considered long-term outcomes. The studies of MDC (case series) provide weak evidence that MDC may alter treatment patterns. Several population-based cohort studies showed that related aspects of team work, specialist (surgeon) and hospital workload and specialisation, are associated with improved survival. This group of studies used better quality design with more clearly defined outcome measures, and most of the studies have allowed for possible confounding variables. Evidence of a survival benefit was most consistent for specialist (surgeon) effect. However, the reasons behind the improved survival reported in these studies are unclear, and it is unlikely that this is entirely attributable to treatment patterns. We conclude that although intrinsically multidisciplinary care should be associated with better survival, there remains a paucity of evidence to support this. Studies of the long-term clinical effects of MDC in breast cancer should be a priority for future evaluation.     

乳腺磁共振在乳腺癌诊断治疗中的运用

乳腺MRI具有很好的软组织分辨率和无射线辐射等优点,对乳腺癌的早期诊断和局部分期明显优于乳腺X线摄影和超声检查。随着乳腺癌个体化、规范化综合治疗理念的推广,乳腺MRI在综合治疗中的作用日益受到重视,伴随对乳腺MRI临床应用的开展和研究的深入,其在乳腺癌分期中的评估、保乳手术病例术前的筛选、腋窝淋巴结转移原发不明者的诊断、新辅助化疗(neoadjuvant chemotherapy, NAC)的疗效评估、随访监测中的应用价值也得到了很好的评估。同时,乳腺MRI对肿瘤范围的客观准确的评估也是正确选择治疗方式的依据。     

1例转移性隐匿性乳腺癌的临床诊治

隐匿性乳腺癌(occult breast cancer, OBC), 是较少见的特殊类型乳腺癌, 指经临床体检和影像学检查未发现乳房内包块而以腋窝淋巴结转移或其他远处转移为首发症状, 并经病理证实来源于乳腺组织的乳腺癌。对转移淋巴结进行组织病理学检查是OBC诊断的关键。对于钼靶和超声阴性的OBC, 增强核磁共振(MRI)检查在寻找原发灶方面有重要作用, 且有助于OBC的术前定位和指导手术方案。其手术治疗方法的选择尚有争议。现介绍1例晚期转移性OBC, 经多学科联合诊治、予以个体化综合治疗的成功经验, 为OBC的诊治提供更多思路, 强调多学科协作诊疗模式。      

Neoadjuvant systemic treatment of breast cancer

Neoadjuvant systemic breast cancer therapy is the administration of systemic therapy to eligible breast cancer patients prior to surgery. This treatment modality was developed out of necessity to downstage inoperable tumors, but it has evolved into a tool for breast conservation surgery. The neoadjuvant approach is also commonly used now to explore the efficacy of new therapeutics by assessing their impact on pathologic complete response or other endpoints. This article will review the foundations of this treatment modality and the latest progress in the field. Considering the heterogeneity of breast cancer, it is clear that no single treatment will fit all types of breast cancer. Thus, there is a need to understand the biological underpinnings of the different types of breast cancer in order to design better treatments that will ultimately improve the eradication rate of this disease.     

Variations in treatment and survival in breast cancer

To achieve optimum quality of care for women with breast cancer in the UK, uniformity of care in accordance with consensus guidelines is needed. This review highlights variations in provision of care for women with breast cancer, with particular emphasis on care received in the UK, examines differences in survival, and discusses the factors that may underlie these differences. Strong variation in treatment was identified, which appeared to affect survival significantly. These findings reinforce the need for women with breast cancer to be treated by dedicated specialists working within a multidisciplinary team to provide a high standard of care.     

Changes in surgical management resulting from case review at a breast cancer multidisciplinary tumor board

BACKGROUND: The treatment of breast cancer requires a multidisciplinary approach, and patients are often referred to a multidisciplinary cancer clinic. The purpose of the current study was to evaluate the impact of this approach on the surgical management of breast cancer. METHODS: The medical records of 149 consecutive patients referred to a multidisciplinary breast cancer clinic over a 1-year period with a diagnosis of breast cancer were reviewed retrospectively for alterations in radiologic, pathologic, surgical, and medical interpretations and the effect that these alterations had on recommendations for surgical management. RESULTS: A review of the imaging studies resulted in changes in interpretations in 67 of the 149 patients studied (45%). This resulted in a change in surgical management in 11% of patients. Review of the pathology resulted in changes in the interpretation for 43 of the 149 patients (29%). Thirteen patients (9%) had surgical management changes made solely as a result of pathologic reinterpretation. In 51 patients (34%), a change in surgical management was recommended after discussion with the surgeons, medical oncologists, and radiation oncologists that was not based on reinterpretation of the radiologic or pathologic findings. Overall, a second evaluation of patients referred to a multidisciplinary tumor board led to changes in the recommendations for surgical management in 77 of 149 of those patients studied (52%). CONCLUSIONS: The changes in management stemmed from differences in mammographic interpretation, pathologic interpretation, and evaluation by medical and radiation oncologists and surgical breast specialists. Multidisciplinary review can provide patients with useful additional information when making difficult treatment decisions.     

Sentinel lymph node biopsy in the management of breast cancer

Sentinel node localization is the second most important development in this century after conservative lumpectomy for the treatment of early breast cancer. The sentinel node mapping is a new multidisciplinary approach for staging of axilla in an accurate and less morbid way as compared to axillary node dissection. Sentinel lymph node biopsy in patients with breast cancer has been adopted rapidly into clinical practice. The accuracy of sentinel lymph node biopsy is more than 95%, when performed meticulously (by an experienced multidisciplinary team) with proper patient selection. Sentinel lymph node biopsy is most widely used for both palpable and non-palpable T1 and T2 tumors. Recent studies show application of sentinel lymph node technique in patients with locally advanced breast cancer and after neoadjuvant chemotherapy. Therefore, sentinel lymph node biopsy technique has application in developing countries and other countries where screening for breast cancer is not common and most patients present relatively in advanced stage of the disease. Several aspects of the sentinel lymph node biopsy including technique, case selection, pathologic analysis and accuracy with supportive important studies published in the literature will be discussed in this review.     

Medical treatment for older breast cancer patients

The incidence of breast cancer and the percentage of the population 65 years of age or older is increasing in Japan. So many elderly patients with breast cancer are given medical treatment. The first-line treatment for elderly patients with hormone responsiveness is endocrine therapy prior to cytotoxic chemotherapy in principle. In terms of chemotherapy, treatment for elderly patients should not be avoided simply because of their age. Oncologists must determine whether chemotherapy should be prescribed after they assess the benefits and risk, including comorbidity and life expectancy, in elderly patients. In future, combinations with low harm treatments, including biologic agents, should be considered in treatment strategy for elderly patients with breast cancer.