The Role of Capecitabine in Early Stage Breast Cancer

Adjuvant systemic therapy is partly responsible for the decrease in breast cancer mortality we have seen over the past two decades. Hormonal therapy and combination chemotherapy based on anthracyclines and taxanes represent the best current approach for early breast cancer patients. Primary as well as secondary development of resistance represents the major challenges to improve our results. Major benefits have been achieved as we recognized populations with particular molecular abnormalities (HER2 positive) and applied specific targeted agents (trastuzumab). However, the addition of other traditional chemotherapy agents has remained a challenge. With consistent data both as a single agent and as part of combinations in the treatment of advanced disease, capecitabine is being explored in over 20,000 early breast cancer patients currently participating in clinical trials. In this review, we discuss the available evidence for the incorporation of capecitabine in the (neo)-adjuvant treatment of patients with breast cancer.     

Current status of endocrine therapy for breast cancer

Endocrine therapy is usually indicated prior to chemotherapy as the first line therapy for metastatic breast cancer patients because of its milder toxicity. Patients who respond to a first-line endocrine therapy have a high chance of responding to a second-line endocrine therapy, and thus the responders to a first-line endocrine therapy would better be treated with second or third-line endocrine therapy. In the adjuvant setting, tamoxifen (antiestrogen) has been proven to improve the prognosis of both pre- and postmenopausal estrogen receptor positive breast cancer patients, and goserelin (LH-RH agonist) has been proven to improve prognosis in premenopausal women comparable to chemotherapy (CMF). Very recently, preliminary results have indicated that anastrozole (aromatase inhibitor) is superior to tamoxifen as adjuvant treatment for estrogen receptor positive postmenopausal breast cancer patients. In addition, the recent success of tamoxifen in a chemoprevention trial seems to have ushered in a new era wherein prevention of breast cancer is much more emphasized than treatment of established breast cancer.     

Is There Still a Role for Axillary Dissection in Breast Cancer Surgery?

The operative management of breast cancer has followed a natural progression toward less invasive techniques over the past century as chemotherapy, hormonal therapy, and radiation therapy have become more effective and used more frequently. Sentinel lymph node (SLN) biopsy in clinically node-negative patients has replaced axillary lymph node dissection (ALND), resulting in improved staging and decreased morbidity. ALND has remained important for patients with clinically involved lymph nodes or positive SLN; however, new evidence from the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial has identified a subset of patients with breast cancer who do not benefit from axillary lymphadenectomy following a positive SLN biopsy. These results are practice changing and need to be analyzed within the context of patient selection and multidisciplinary treatment. Herein, we review the emerging data regarding the benefits and indications for axillary lymphadenectomy in the modern era of multidisciplinary breast cancer management.     

Mechanisms and strategies to overcome chemotherapy resistance in metastatic breast cancer

Resistance to chemotherapeutic agents is a significant issue in the management of patients with breast cancer. Anthracyclines, although first used over 30 years ago, are still part of the standard chemotherapy for this disease. Subsequently, the taxanes heralded a new era in chemotherapy and have been used extensively in the treatment of metastatic breast cancer. Unfortunately, along with other constituents of combination chemotherapy for metastatic breast cancer such as cyclophosphamide, these agents become increasingly ineffective in progressive disease and tumours are then deemed to be drug resistant - frequently multidrug resistant. A number of processes have been identified that can underlie clinical drug resistance, and these largely stem from in vitro laboratory-based studies in human cancer cell lines. A large proportion of these studies have focused on multidrug resistance associated with resistance to natural product anticancer agents due to the presence of putative drug transporter proteins such as P-glycoprotein, MRP1, and BCRP. Other studies have highlighted mechanisms whereby breast cancer cells show resistance to chemotherapeutic agents by altered regulation of DNA repair processes, with many other factors influencing drug detoxification processes and altering drug targets. New developmental agents with improved specificity for tumour cells, such as trastuzumab, and those with low susceptibility to common tumour-resistance mechanisms, such as ixabepilone, have provided new hope for effective treatment of breast cancer. Ixabepilone is the first in a new class of neoplastics, the epothilones. With these developments in therapy, and the technology of gene expression profiling, the future holds more promise for the development of more effective treatment for metastatic breast cancer.     

Targeting metabolism in breast cancer: How far we can go?

Adjuvant therapies for breast cancer have achieved great success in recent years and early breast cancer is now a curable or chronic disease. Targeted therapies, including endocrine therapy and human epidermal growth factor receptor-2 targeted therapy, marked a new era of breast cancer treatment. However, except for chemotherapy, an efficient drug treatment to improve the overall survival of breast cancer patients is still lacking for triple negative breast cancer. Furthermore, a certain proportion of breast cancer patients present with resistance to drug therapy, making it much more difficult to control the deterioration of the disease. Recently, altered energy metabolism has become one of the hallmarks of cancer, including breast cancer, and it may be linked to drug resistance. Targeting cellular metabolism is becoming a promising strategy to overcome drug resistance in cancer therapy. This review discusses metabolic reprogramming in breast cancer and the possible complex mechanism of modulation. We also summarize the recent advances in metabolic therapy targeted glycolysis, glutaminolysis and fatty acids synthesis in breast cancer.     

Emerging gene-based prognostic tools in early breast cancer: First steps to personalised medicine

Breast cancer remains a major cause of neoplastic disease in much of the developed world. The majority of cases are diagnosed with oestrogen receptor (ER)-positive and human epidermal growth factor receptor-2 negative invasive ductal carcinoma and are treated predominantly by surgery which includes sentinel node biopsy and adjuvant endocrine therapy ± adjuvant radiotherapy. It is believed that an indeterminate subset of the patient population is needlessly incurring chemotherapy related morbidity without attaining any increase in survival due to therapy. Furthermore in the era of extended adjuvant endocrine therapy it is important to identify those patients who can be safely treated with 5 years rather than 10 years of endocrine therapy thus optimising the benefit-risk balance. This perception has propelled the development of more personalised prognostic tools for newly diagnosed cases of ER-positive breast cancer. In this article, we shall review the evidence regarding the currently available gene assays for human breast cancer.     

Primary (neoadjuvant) chemotherapy with docetaxel in breast cancer

The use of primary or neoadjuvant chemotherapy for locally advanced breast cancer, including those patients with inflammatory breast cancer, is well established. The use of primary chemotherapy has also been investigated in patients with operable breast cancer. The potential benefit of using primary chemotherapy is the opportunity to administer systemic therapy at an earlier timepoint, where it may be more effective against microscopic disease. In addition, primary chemotherapy for patients with operable breast cancer may also result in higher rates of breast conservation, axillary nodal downstaging, and potential improvement in patient outcome. A variety of different chemotherapy drugs have been evaluated in the primary chemotherapy setting. One of the most common approaches is to use an anthracycline-based regimen for 4 or more cycles of treatment before considering definitive local therapy. Although high tumor response rates have been reported using anthracycline-based regimens, the fraction of patients actually attaining a pathologic complete response has remained small (less than 20%). With the introduction of new chemotherapy drugs, such as docetaxel, which is associated with a very high tumor response rate in metastatic disease, a natural evolution of clinical investigation is to use docetaxel in the neoadjuvant or primary chemotherapy setting. Some of the recent trials that have evaluated single-agent docetaxel, docetaxel-based chemotherapy combinations, and novel sequencing strategies that include docetaxel in the neoadjuvant setting are reviewed. The results from these trials clearly suggest that docetaxel-containing treatment strategies can be considered a standard in the primary chemotherapy setting     

Anthracycline vs nonanthracycline adjuvant therapy for breast cancer

The treatment of breast cancer has progressed substantially over the past 15 years. Data from randomized adjuvant trials have shown that the risk of disease recurrence and death is significantly reduced when adjuvant chemotherapy and/or hormonal therapy is added to treatment. As new strategies are incorporated, one of the continued controversies in patient management is whether adjuvant anthracyclines should be the preferred treatment for all patients. Data from randomized and translational clinical trials have become available and are helping to elucidate the proper role of anthracyclines, as well as their acute and long-term toxicities. In most situations, an anthracycline is currently preferred, but other single and combination chemotherapies are currently under evaluation and appear promising for use in the adjuvant setting. Continued breast cancer research using molecular markers (such as topoisomerase II-alpha and gene clusters) as predictors of treatment response, could help individualize decisions regarding whether to incorporate anthracyclines into adjuvant therapy regimens.     

High-dose chemotherapy and autologous bone marrow or stem cell reconstitution for solid tumors

High-dose chemotherapy—in conjunction with the transplantation of either mononuclear cells harvested from the marrow or CD 34+ cells harvested from the peripheral blood—has proved effective in curing certain patients with leukemia, lymphoma, and, to a lesser extent, multiple myeloma. Though the CD 34+ therapy is a relatively new treatment and the mononuclear cell therapy is more standard, both have been successfully used to reconstitute lethally damaged hematopoietic stem cells. Allogeneic transplants have been more effective than autologous transplants against tumors, but they also pose a greater hazard of death from complications, graft-versus-host disease, and infections. More currently, this approach has been used in patients with certain solid tumors, either in a metastatic or recurrent disease setting or as an adjuvant to surgery and/or standard doses of chemotherapy in patients with a known high risk of recurrence.Unfortunately, the majority of the studies about the impact of this therapy have been small and nonrandomized against standard therapy, and they have encompassed diverse populations of patients. This makes comparisons with contemporary standard—dose approaches—already problematic from a statistical point of view—even more dangerous because of the dissimilarity of the groups being compared. Particularly in the high-risk adjuvant setting, data suggest that those patients that meet the eligibility criteria for high-dose therapy and transplantation exhibit the prognostic factors for a positive outcome. When one compares these results with those of a more heterogeneous group of patients treated with conventional therapy, the conclusion might be drawn that high-dose therapy is superior to standard therapy, when a longer follow-up of the patients in the study will show this to be untrue. Thus there is a plea from clinicians and physicians conducting trials for prospective, randomized trials that would allow a fair comparison between high-dose therapy in combination with transplant procedures and a more conventional, standard chemotherapy, which is often less toxic and definitely less expensive.This article reviews the data for transplantation in four tumors: breast cancer, ovarian cancer, small-cell lung cancer, and germ cell testis cancer. There is such a small number of randomized trials that an attempt must be made to compare these small high-dose therapy studies with similar, though not identical, large studies of conventional therapy. This article attempts to make those comparisons, and several conclusions are drawn, which are detailed below.First, few data support the use of high-dose chemotherapy in any patient with recurrent and drug-resistant breast cancer or ovarian cancer. Similarly, few data support the use of high-dose approaches for patients with extensive small-cell lung cancer. For patients with metastatic breast cancer that has responded completely to conventional chemotherapy, no data suggest a survival advantage for the immediate consolidation of that response with high-dose chemotherapy. The only trial addressing this issue found that immediate transplantation led to a better disease-free survival rate, but overall survival, as compared with that of patients who received transplants at relapse, was not affected, and the study did not address the issue of the relative merits of conventional chemotherapy in either case. The only study of high-dose versus conventional chemotherapy was statistically underpowered, and it showed poorer-than-anticipated outcomes in the patients who received conventional therapy. Ongoing or recently completed trials will, it is hoped, address the many unanswered questions in this area.For patients with high-risk, non-metastatic breast cancer, no completed and analyzed phase III randomized studies address the relative merits of conventional versus high-dose therapy. Early results from high-dose approaches suggest a better disease-free survival than has typically been observed with standard chemotherapy, but the patients who have received transplants are often highly selected and may have favorable prognostic factors as compared with the more heterogeneous groups that have received conventional therapy over the years. Several trials underway address the value of high-dose therapy in early stage, high-risk breast cancer patients (the group most likely to benefit from this type of therapy, based on the knowledge gleaned from the studies of transplants in patients with hematologic tumors), and these results are anxiously awaited by patients and health care professionals alike.In ovarian cancer, where high-dose chemotherapy and transplantation is becoming increasingly more common, many small phase II trials have shown high response rates but short response durations, and the data currently available make it difficult to maintain enthusiasm for this approach in patients with drug-resistant or large-volume disease. Several trials underway randomized patients with demonstrated drug sensitivity and a low volume of tumors (achieved either surgically or with conventional chemotherapy) to receive either high-dose therapy or more conventional consolidation approaches. Until these trials are complete, the value of high-dose therapy will remain unknown.There are little data regarding transplantation in patients with limited-stage small-cell lung cancer. A single randomized trial demonstrated an outcome advantage for high-dose therapy, but the patient numbers were too small to allow any definitive conclusions to be made. Large randomized trials in this population are needed to address the value of high-dose approaches. The preferred population in which to perform these trials would be patients with limited disease who respond to initial conventional chemotherapy and are subsequently randomized to receive conventional consolidation with chest and cranial radiation or high-dose therapy with the same radiation. Survival would be the only pertinent endpoint. No trials of this sort are currently underway.For patients with testis cancer, data suggest a clear survival benefit from high-dose chemotherapy and transplantation. Two groups of patients still have very poor outcomes—those with mediastinal primary disease and those who progress or relapse within 4 weeks of completion of standard, cisplatin-based therapy. It is unclear if high-dose approaches can salvage these patients. However, in patients whose disease recurs at a point more distant from conventional therapy, there is a potential for a long-term, disease-free survival rate that may be as much as or more than 50% better than that of patients who have been treated with conventional salvage approaches. Finally, it is now possible to identify patients who are at a high risk of a poor outcome and who are candidates for high-dose approaches as part of initial therapy. These patients are currently being studied in an intergroup, randomized trial.     

激素受体阳性早期乳腺癌治疗现状与挑战

在早期发现、有效治疗的情况下,早期乳腺癌是可治愈的,长期无病生存应是早期患者所追求的治疗目标。既往认为乳腺癌各亚型中激素受体（hormone receptor,HR）阳性早期乳腺癌预后最好,然而随着人类表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）阳性乳腺癌抗HER2靶向治疗和三阴性乳腺癌强化治疗的发展,HR阳性早期乳腺癌预后优势已不再明显。当前,术后应用他莫昔芬或芳香化酶抑制单药进行内分泌治疗是HR阳性早期乳腺癌核心辅助治疗方式,但部分患者复发风险高、长期生存情况并不乐观。为改善患者预后、提高生活质量,目前临床主要探索方向包括以下三方面：① 强化治疗。强化方式包括延长内分泌治疗、联合卵巢功能抑制等,近期研究还探索了细胞周期蛋白依赖性激酶4/6抑制剂用于HR阳性早期乳腺癌患者强化治疗的效果和安全性。同时,如何有效地辨别适合于强化治疗的高危患者亦是研究热点,乳腺癌指数、STEPP分析等已获得权威指南推荐用于辅助强化治疗决策。② 化疗降阶/免化疗：精准化疗是目前国际主流趋势,多个国际指南推荐使用多基因检测工具如MammaPrint ^® 、Oncotype DX ^® 、EndoPredict ^® 等分析结果辅助决策化疗降阶,以避免过度治疗。这些检测工具在我国患者中的临床研究和应用也日益增加,有望帮助提升我国患者获益。③ 术前内分泌治疗：尽管术前内分泌治疗可否给HR阳性早期乳腺癌患者带来直接获益尚待确认,但治疗过程中的生化指标变化与患者预后密切相关,或可在后续治疗决策（如是否可免除化疗、是否适用细胞周期蛋白依赖性激酶4/6抑制剂等）中发挥重要的指导作用,值得临床积极探索。本文将就上述HR阳性早期乳腺癌治疗的现状和研究进展进行综述和探讨,以期为临床医生提供参考。     

Changes to Adjuvant Systemic Therapy in Breast Cancer: A Decade in Review

Breast cancer is the second most common cause of cancer death in women among the United States. Fortunately, it continues to be an active area of research. Today, it is well recognized that breast cancer can often be a systemic disease, with micrometastatic involvement at diagnosis in many patients. Over the past decade, adjuvant systemic therapy has been used to eradicate micrometastatic disease, and it has been shown to decrease the rates of recurrence and improve the survival of patients with early-stage, resected breast cancer. Some of the success of modern adjuvant systemic therapy has come from the advent of new chemotherapy and endocrine agents but also from the development of targeted therapies, which have improved the efficacy of conventional, cytotoxic therapy. There has also been increasing awareness that the dosing and schedule of administration of systemic therapies are equally important factors in achieving better outcomes in patients with early-stage breast cancer. Growing research into the biology and genomics of breast cancer has fueled the development of more accurate risk stratification tools and helped individualize the decision to recommend adjuvant systemic therapy. Herein, we present a review of salient developments over the past decade that have helped shape the adjuvant systemic therapy of today.     

Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer

Background

Trastuzumab therapy given in combination with one of several chemotherapy regimens is currently considered the standard of care for the treatment of early-stage, human epidermal growth factor receptor-2 (HER2) -positive breast cancer. The treatment with trastuzumab is due to a significant impact on the survival part of the standard adjuvant treatment of patients with HER2-positive breast cancer. Patients treated with postoperative breast or chest wall irradiation receive trastuzumab concomitant with radiotherapy. In a small proportion of patients trastuzumab causes cardiotoxicity. Preclinical findings indicate a radiosensibilizing effect of trastuzumab in breast cancer cells, but it is not yet clear whether it radiosensibilizes cells of healthy tissues too.

Conclusions

Special attention is required when left breast or left thoracic wall is irradiated in patient receiving trastuzumab, because long-term effects of the concurrent treatment with trastuzumab and radiotherapy are not yet known. In an era where more patients are surviving a diagnosis of breast cancer, better understanding and earlier detection of therapy-induced cardiac toxicity will be of paramount importance.     

New developments in chemotherapy for advanced non-small cell lung cancer

PURPOSE OF REVIEW: The treatment of patients with advanced non-small cell lung cancer has changed considerably in the past decade. This paper reviews the most significant changes seen in chemotherapy and the most promising new agents in development for this disease. RECENT FINDINGS: Chemotherapy prolongs survival and improves quality of life in patients with a good performance status and appears to alleviate disease-related symptoms in patients with a lower performance status. Platinum-based regimens became standard; none of the third-generation drug combinations seemed to be superior to the others. Nonplatinum combinations are reasonable alternatives now and offer a better toxicity profile in certain populations. Attempts to add molecular-targeted therapy to combination chemotherapy have failed except for bevacizumab. New compounds such as pemetrexed, bortezomib, TLK286, bevacizumab, and the epothilones are currently being evaluated in non-small cell lung cancer. SUMMARY: Management of non-small cell lung cancer has improved considerably in the past decade. The overall benefit of chemotherapy over supportive care has been shown, platinum-based doublets have been established, nonplatinum regimens have been developed, chemotherapy has been used more broadly in subgroups of patients who have been previously neglected, and a shorter chemotherapy duration has been shown to be equally effective. After hitting a plateau in the benefit of chemotherapy, new drugs with novel action mechanisms such as the ones described here offer hope to improve therapy for this disease.     

乳腺癌血清肿瘤标志物和循环肿瘤细胞检测的研究进展

 随着分子生物学的发展,乳腺癌的治疗正逐步进入分子分型治疗的时代,为了给患者提供更加有效的个体化治疗,研究者们不断努力寻找乳腺癌新的治疗靶点、疾病监控指标以及疗效预测和预后评估的指标,日益深入的研究显示血清肿瘤标志物和循环肿瘤细胞的检测在乳腺癌治疗中有重要价值。现就近年乳腺癌血清肿瘤标志物和循环肿瘤细胞检测的相关临床研究作一综述。     

Postmenopausal Metastatic Breast Cancer

Endocrine therapy and chemotherapy play important roles in the management of postmenopausal women with metastatic breast cancer. This paper specifically reviews the indications and options for first-line treatment of metastatic breast cancer and recent advances are highlighted, with particular attention to randomized, controlled, phase III clinical trials. Until recently, tamoxifen was standard first-line endocrine treatment for patients with metastatic breast cancer. Now, potent third generation aromatase inhibitors, such as letrozole and anastrozole, have shown superiority to tamoxifen as first-line endocrine treatment and provide an alternative for postmenopausal women. The most active chemotherapy agents for patients with advanced breast cancer have, until recently, been the anthracyclines, doxorubicin and epirubicin. However, their increasing use in the adjuvant setting has resulted in a need for novel active non-cross-resistant cytotoxic drugs for metastatic breast cancer. Real progress has been made with the introduction of the taxanes, paclitaxel and docetaxel. Other developments include the use of single agent cytotoxics such as vinorelbine, the oral fluoropyrimidine capecitabine and gemcitabine, all of which have some activity following either taxanes or anthracyclines, along with a low toxicity profile. Bisphosphonates are bone-specific palliative treatments that have been instituted on the basis of their impact on symptoms and skeletal related morbidity. Finally, the era of biological therapy in the clinic for patients with breast cancer has been heralded with the development and introduction of trastuzumab, a humanized monoclonal antibody which targets the cell surface growth factor receptor HER2/neu. Importantly, each of these new treatment options has provided an incremental improvement in efficacy over previous standard first-line therapies.     

Symptom clusters in cancer patients: a review of the literature

Cancer patients often experience multiple symptoms, and those symptoms can independently predict changes in patient function, treatment failures, and post-therapeutic outcomes. Symptom clusters are defined as two or more concurrent symptoms that are related and may or may not have a common cause. The purpose of the present study was to review, in cancer patients, common symptom clusters and their predictors.Using MEDLINE, EMBASE, Cochrane Central, and CINAHL, we conducted a literature search on symptom clusters in cancer patients. Studies that investigated predetermined clusters were not included. We identified seven individual studies and one group of five studies validating the M.D. Anderson Symptom Inventory. These studies had been published between 1997 and 2006. Two of the seven individual studies and the group of five studies that had validated the M.D. Anderson Symptom Inventory included patients with any cancer type; three studies included breast cancer patients only; and two studies included lung cancer patients only.A gastrointestinal cluster consisting of nausea and vomiting was the single cluster common to two of the studies. The severity of this cluster increased when patients were treated with chemotherapy. No common clusters were found in the lung and breast cancer patient populations. However, breast cancer patients experienced more symptom cluster involvement while undergoing chemotherapy. We noted methodology disparities among the papers with regard to assessment tools used, statistical analyses, and populations.Research on symptom clusters is still in an early stage. Multiple symptoms clearly affect prognosis, quality of life, and functional status. The study of symptom clusters is important for its implications regarding patient management, and a consensus on appropriate research methodology is vital.     

Dose intensity as a therapeutic strategy in breast cancer

The results of systemic treatment for primary and metastatic breast cancer have plateaued in the past decade. The majority of oncologists continue to use the same chemotherapy regimens and endocrine therapies that were available in the mid 1970s. In metastatic breast cancer, still only 60–70% of patients can be expected to achieve a remission, with only 10–20% of these being a complete remission, which is usually of short duration. Metastatic breast cancer remains incurable today. Obviously, new treatment strategies are needed. The development of new active drugs, or the development of innovative ways of giving old drugs, has been disappointing in breast cancer. Similarly, combining hormones with chemotherapy, or the use of various biologic response modifiers, has not resulted in a major advance. One strategy that is currently undergoing active research is increased dose intensity of chemotherapy. This can be achieved by delivering extremely high doses of cytotoxic chemotherapy followed by hematopoietic support. A second approach involves delivering lower doses, but on a more frequent schedule than conventional programs. Preliminary results from phase II evaluation of these programs demonstrate high complete response rates, relatively short response durations, and considerable toxicity. However, 10–20% of patients treated with these regimens remain in complete remission several years after treatment, providing optimism that this approach may be effective in some patients. Advances in hematopoietic support, including autologous bone marrow transplantation (ABMT), peripheral stem cell administration, and the use of hematopoietic growth factors, have reduced toxicity. This strategy is now ready for phase III randomized trials in metastatic breast cancer as well as in the high-risk adjuvant patient to determine if high-dose therapy offers a worthwhile advantage in patients with breast cancer.     

Research needs in breast cancer

New research questions emerge as medical needs continue to evolve and as we improve our understanding of cancer biology and treatment of malignancies. Although significant advances have been made in some areas of breast cancer research resulting in improvements in therapies and outcomes over the last few decades, other areas have not benefited to the same degree and we continue to have many gaps in our knowledge. This article summarizes the 12 short and medium-term clinical research needs in breast cancer deemed as priorities in 2016 by a panel of experts, in an attempt to focus and accelerate future research in the most needed areas: (i) de-escalate breast cancer therapies in early breast cancer without sacrificing outcomes; (ii) explore optimal adjuvant treatment durations; (iii) develop better tools and strategies to identify patients with genetic predisposition; (iv) improve care in young patients with breast cancer; (v) develop tools to speed up drug development in biomarker-defined populations; (vi) identify and validate targets that mediate resistance to chemotherapy, endocrine therapy and anti-HER2 therapies; (vii) evaluate the efficacy of local-regional treatments for metastatic disease; (viii) better define the optimal sequence of treatments in the metastatic setting; (ix) evaluate the clinical impact of intra-patient heterogeneity (intra-tumor, inter-tumor and inter-lesion heterogeneity); (x) better understand the biology and identify new targets in triple-negative breast cancer; (xi) better understand immune surveillance in breast cancer and further develop immunotherapies; and (xii) increase survivorship research efforts including supportive care and quality of life.     

Clinical application of molecular profiling in breast cancer

Breast cancer is the leading type of cancer and second leading cause of cancer death in women. Breast cancer mortality has declined over the past 10 years largely due to early detection by mammographic screening, but also in part due to the increasing use of adjuvant hormonal therapy and chemotherapy. Indications for adjuvant chemotherapy have now expanded to include women who are at low risk of recurrence, resulting in overtreatment of most women to benefit a few, particularly those with favorable clinical features. New techniques have been evaluated that identify specific molecular signatures that may more accurately predict prognosis than clinical features, and that may also identify individuals who are more likely to benefit from endocrine therapy and/or chemotherapy. This review will focus on the clinical applications of these novel techniques reported to date, and how this may lead to the incorporation of molecular diagnostics into clinical practice. Two prospective, multicenter, multinational Phase III trials evaluating tumor genomic profiling in breast cancer are currently in development, and will be initiated within the forthcoming year. The completion of these important studies will represent the first step toward integrating molecular profiling into treatment selection for adjuvant therapy in breast cancer.