SEARCH

SEARCH BY CITATION

Keywords:

  • Asia–Pacific;
  • breast cancer;
  • clinical trials;
  • treatment guidelines

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MANAGEMENT OF METASTATIC BREAST CANCER
  5. CLINICAL EXPERIENCE IN ASIA–PACIFIC REGION
  6. CLINICAL TRIALS IN ASIA–PACIFIC POPULATIONS
  7. NEED FOR ASIA–PACIFIC TREATMENT GUIDELINES
  8. CONCLUSION
  9. REFERENCES

There is an urgent need to identify the best ways to manage breast cancer in women in the Asia–Pacific region. It is increasingly recognized that disease patterns, efficacy and toxicities of various treatment regimens, differ between Asia–Pacific women and women in the West. Despite these differences, breast cancer treatment in the Asia–Pacific region often follows evidence-based treatment guidelines based on Western clinical trials. To obtain the best possible outcomes in the Asia–Pacific region, country-specific breast cancer clinical trials and registries are crucial. Findings should be integrated into country-specific consensus treatment guidelines. These measures would facilitate the best choice of drugs, the optimal doses, and the optimal schedules for treating women with breast cancer in the Asia–Pacific region.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MANAGEMENT OF METASTATIC BREAST CANCER
  5. CLINICAL EXPERIENCE IN ASIA–PACIFIC REGION
  6. CLINICAL TRIALS IN ASIA–PACIFIC POPULATIONS
  7. NEED FOR ASIA–PACIFIC TREATMENT GUIDELINES
  8. CONCLUSION
  9. REFERENCES

Over the past five years, breast cancer prevention, treatment and survival outcomes have improved substantially throughout the world.1 Advances in understanding the molecular etiology of breast cancer have led to the development of more effective treatment regimens with improved tolerability profiles.2 In the Asia–Pacific region, the rising burden of breast cancer has resulted in the implementation of national screening programs and efforts to improve disease management, as clinical data on new agents and regimens have become available. The integration of treatment guidelines for breast cancer, the development of cancer registries and the increased participation of cross-disciplinary health-care providers are also helping to improve care. For example, a significant improvement in overall survival after distant metastases in women with breast cancer (P = 0.0228) was observed between the years 1995–2000 and 2001–2005 at the Chang Gung Memorial Hospital in Taiwan (Dr YC Lin, personal communication).

However, it is becoming increasingly evident that breast cancer is a heterogeneous disease. Evidence from clinical studies indicates that substantial differences exist between Asian and Western women with respect to their molecular phenotype and the natural course of the disease, which effects their responsiveness to and toleration of treatment.3–7 One's ethnic background may contribute to the molecular diversity of breast cancer.8,9 Differences in the toleration of chemotherapeutic agents have been reported between Asia–Pacific and Western women.10–12 As a result, it may not be possible to extrapolate safety results, dosing schedules, and efficacy data from large randomized trials that primarily involve Western women only.

This review examines the management of metastatic breast cancer, the importance of increasing patient participation in clinical trials, and developing treatment guidelines to optimize breast cancer treatment in the Asia–Pacific region. Strategies for overcoming the barriers to implementing these initiatives in countries with limited resources are discussed.

MANAGEMENT OF METASTATIC BREAST CANCER

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MANAGEMENT OF METASTATIC BREAST CANCER
  5. CLINICAL EXPERIENCE IN ASIA–PACIFIC REGION
  6. CLINICAL TRIALS IN ASIA–PACIFIC POPULATIONS
  7. NEED FOR ASIA–PACIFIC TREATMENT GUIDELINES
  8. CONCLUSION
  9. REFERENCES

Although the etiology and natural history of breast cancer appears to differ between Asia–Pacific women and Western women, the main goals of treatment are similar: to prolong life, to prevent and relieve symptoms and to maintain the patient's quality of life. Depending on the features of the disease and the clinical characteristics of the patient, treatment options for metastatic breast cancer include surgery, endocrine therapy, chemotherapy, targeted therapy and supportive treatments, such as radiotherapy and bisphosphonate therapy.2

Resection of the primary tumor is not routinely advised for patients with metastatic breast cancer at diagnosis because the disease is considered incurable. Recent reports, however, indicate that the complete surgical excision of the primary tumor improves patient survival.13–17 Candidates for curative surgery in patients with metastatic breast cancer that exhibited an isolated metastasis, have a good performance status and have achieved a long disease-free interval following the treatment of the primary tumor. A review of five-year outcomes for patients with breast cancer treated with surgery, with or without chemotherapy, showed survival rates of 35–80% in patients with isolated metastases to the lung18–20 and 22–46% in patients with isolated metastasis to the liver.21–24 For patients with isolated metastases to the brain who were treated with surgery, with or without whole-brain irradiation, five-year survival ranged from 7–38%.25–27 Additionally, in patients with supraclavicular lymph node metastases, overall survival and distant metastasis-free survival is related to the number of positive axillary lymph nodes.28 Univariate analysis of overall survival after supraclavicular lymph node metastasis showed significant improvements in five-year survival rates with surgery (P = 0.0327) and neck control (P = 0.0136), but not with chemotherapy, radiotherapy or hormonal therapy.28

The choice of systemic treatment for metastatic breast cancer is based on factors such as previously used drugs, pre-existing toxicities, the disease-free interval and biomarkers such as estrogen and progesterone receptors and HER2/neu status. The use of endocrine therapy can provide long (>2 years) progression-free survival for women with hormone receptor-positive tumors, no visceral metastases and limited disease-related symptoms. For previously untreated metastatic breast cancer, standard chemotherapy regimens include anthracycline and a taxane.2 Compared with the sequential use of single chemotherapeutic agents, combination chemotherapy regimens are associated with significant advantages for tumor response and time to progression, and provide a modest improvement in overall survival.2,29 The addition of trastuzumab to first-line chemotherapy combination regimens is used for HER2/neu-positive tumors. This combination has been shown to increase time to progression and overall survival compared with chemotherapy alone for these patients.2 In estrogen receptor-positive tumors, the maintenance of endocrine therapy can provide good disease control following chemotherapy.2

CLINICAL EXPERIENCE IN ASIA–PACIFIC REGION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MANAGEMENT OF METASTATIC BREAST CANCER
  5. CLINICAL EXPERIENCE IN ASIA–PACIFIC REGION
  6. CLINICAL TRIALS IN ASIA–PACIFIC POPULATIONS
  7. NEED FOR ASIA–PACIFIC TREATMENT GUIDELINES
  8. CONCLUSION
  9. REFERENCES

To date, the clinical experience with available systemic treatment in the Asia–Pacific women is variable due to the small number of clinical studies conducted in the region. It is increasingly recognized that disease patterns, as well as the efficacy and toxicities of various treatment regimens, may differ between Asia–Pacific and Western women.10–12 Consequently, dosing regimens and tolerability profiles reported in large, randomized clinical trials involving mainly Caucasian women may not be consistent with clinical practice experience in the Asia–Pacific region. For example, in Asia–Pacific women the use of docetaxel is associated with lower toxicity than that reported in clinical trials involving mainly Caucasian women. Differences in body composition and drug metabolism may alter the pharmacokinetics of chemotherapeutic agents between ethnic groups. Additionally, the use of Chinese herbal therapy by a large percentage of Asian patients is associated with the potential for drug–drug interactions and other side effects. Accordingly, an urgent need exists to conduct clinical trials in Asia–Pacific populations to further identify unique features of the disease, treatment and outcomes for Asia–Pacific women with breast cancer.

CLINICAL TRIALS IN ASIA–PACIFIC POPULATIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MANAGEMENT OF METASTATIC BREAST CANCER
  5. CLINICAL EXPERIENCE IN ASIA–PACIFIC REGION
  6. CLINICAL TRIALS IN ASIA–PACIFIC POPULATIONS
  7. NEED FOR ASIA–PACIFIC TREATMENT GUIDELINES
  8. CONCLUSION
  9. REFERENCES

Several new chemotherapeutic drugs and targeted therapies are under investigation at the time of writing for the first-line and second-line treatment of breast cancer, either alone or in combination. There is an urgent need for countries in the Asia–Pacific region to run their own clinical trials to increase clinical data and experience and address their unique needs. At the time of writing, a considerable lag time exists in the clinical development and licensing of new breast cancer agents in the Asia–Pacific region.

In Japan, for example, there is usually a delay of >4 years in the availability of new drugs after their approval in the USA or the EU due to the strict criteria for accepting clinical data from non-Japanese patients. Currently clinical trial registries exist for Japan, Australia, China and India. A search of these registries shows the number of clinical trials for breast cancer is increasing in the Asia–Pacific region, particularly in Japan (Table 1). Many of these clinical studies investigate the effect of dosage and schedule modifications on clinical response rates and the toxicity of existing treatment regimens in Asian women with breast cancer. For example, recently completed phase II trials conducted at Chang Gung Memorial Hospital in Taiwan included studies of cisplatin/taxane and epirubicin/docetaxel combinations and a weekly administration of docetaxel.30–32 Additional studies are needed to assess more recent treatments for breast cancer. Additionally, conclusions from clinical trials conducted in the Asia–Pacific region are often limited by the small numbers of enrolled patients. One strategy for overcoming this barrier may be to increase the enrollment of Asia–Pacific women in international trials and analyze the local data. This strategy may be particularly useful in countries with limited resources for supporting clinical trials.

Table 1.  Clinical trials for breast cancer in the Asia–Pacific region
Study titleStudy numberPhasePatient (N)Country
A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of herceptin + docetaxel + pertuzumab versus herceptin + docetaxel + placebo in patients with locally advanced, inflammatory or early stage breast cancerWO20698II400Singapore, Taiwan, Philippines
BEATRICE study: A study of Avastin (bevacizumab) adjuvant therapy in triple negative breast cancerBO20289III2530Singapore, Taiwan, Thailand, Philippines
Neoadjuvant study of AC followed by ixabepilone or paclitaxel in early stage breast cancer that is HER-2 negative and estrogen receptor negative II300Singapore, Taiwan, Philippines, India
Study of herceptin (trastuzumab) in women with metastatic breast cancerWO17299  Taiwan
A randomized, double-blind study of the effect of first line treatment with Avastin (bevacizumab) in combination with docetaxel on progression-free survival and disease response in patients with HER-2 negative metastatic breast cancerBO17708III750Taiwan, Thailand
HERA study: A randomized, open-label study of the effect of herceptin (trastuzumab) on disease-free and overall survival in women with HER-2 positive primary breast cancer who have completed adjuvant chemotherapyBO16348III4482Taiwan, Singapore, Thailand
A randomized, open-label study of the effect of different dosing regimens of Xeloda in combination with Taxotere on disease progression in patients with locally advanced and/or metastatic breast cancerNO16853II440Thailand, India
A randomized, open-label study of the effect of herceptin plus Arimidex compared with Arimidex alone on progression-free survival in patients with HER-2 positive and hormone-receptor positive metastatic breast cancerBO16216III202India
N-SAS BC 06: Randomized phase III study of adjuvant endocrine-therapy with or without chemotherapy for postmenopausal breast cancer patients who responded to neoadjuvant letrozoleUMIN00001090III1700Japan
Randomized study of docetaxel or weekly paclitaxel followed by 5FU + epirubicin + cyclophosphamide as preoperative chemotherapy for primary breast cancer (KBCOG-06)UMIN000000916III200Japan
Investigation of a capecitabine as a postoperative adjuvant chemotherapy in breast cancer patientsUMIN000000843IV400Japan
Phase II study of capecitabine plus paclitaxel combination chemotherapy in patients with metastatic breast cancerUMIN000000869II42Japan
Randomized control study of Xeloda alone versus TS-1 alone as first-line treatment in unresectable or recurrent breast cancer patientsUMIN000000609III220Japan
A randomized multicenter phase 2 trial of neoadjuvant paclitaxel followed by fluorouracil, epirubin, and cyclophosphamide (FEC) with or without estrogen deprivation by LH-RH agonist or aromatase inhibitor in breast cancer larger than 2 cmUMIN000000748II120Japan
Study of combination chemotherapy of CPT-11/S-1 after anthracycline and taxane in recurrent or metastatic breast cancer (JBCRG-M01)UMIN000000517I/II32Japan
Phase I/II study of vinorelbine plus trastuzumab in patients with advanced/recurrent breast cancer previously treated with anthracyclines and taxanesC000000447I/II60Japan

NEED FOR ASIA–PACIFIC TREATMENT GUIDELINES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MANAGEMENT OF METASTATIC BREAST CANCER
  5. CLINICAL EXPERIENCE IN ASIA–PACIFIC REGION
  6. CLINICAL TRIALS IN ASIA–PACIFIC POPULATIONS
  7. NEED FOR ASIA–PACIFIC TREATMENT GUIDELINES
  8. CONCLUSION
  9. REFERENCES

Definite guidelines for the treatment of patients with breast cancer is often lacking in the Asia–Pacific region because of a lack of clinical experience in indigenous populations. In countries with limited resources, breast cancer treatment follows Western guidelines, such as those from the National Comprehensive Cancer Network and the National Cancer Institute.33 However, these guidelines were developed using evidence from large trials in Western women and may not provide adequate evidence for treating Asia–Pacific women. Some countries may also have difficulties with disseminating and implementing treatment guidelines.

The experience at the Chang Gung Memorial Hospital showed that the outcomes of patients with breast cancer have improved noticeably since the availability of new, more effective drugs, and their incorporation into evidence-based treatment guidelines. For example, in patients with stage III breast cancer, the five-year disease-free survival rate was 33.4% between 1995 and 2000 (prior to the guidelines) and 54.6% between 2001 and 2005 (following the publication of the guidelines; P < 0.0001) (written communication S. Chen, May 2008). The five-year overall survival rate increased from 46.8 to 57.6%, respectively, for these intervals (P = 0.0138). To optimize breast cancer treatment in the Asia–Pacific region, every country needs to move toward unified guidelines, or review and modify Western guidelines as appropriate. The development of evidence-based treatment guidelines is one way that even countries with limited resources can improve the treatment of their patients with breast cancer (Box 1).34

Box 1 Developing evidence-based care in countries with limited resources.

  • • 
    Convene evidence-based advice panel
  • • 
    Determine the problems
  • • 
    Conduct a systematic review
  • • 
    Identify data gaps and areas of consensus
  • • 
    Draft proposed treatment guidelines and/or conduct clinical trials
  • • 
    Obtain expert and external reviews
  • • 
    Distribute treatment guidelines and provide education

CONCLUSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MANAGEMENT OF METASTATIC BREAST CANCER
  5. CLINICAL EXPERIENCE IN ASIA–PACIFIC REGION
  6. CLINICAL TRIALS IN ASIA–PACIFIC POPULATIONS
  7. NEED FOR ASIA–PACIFIC TREATMENT GUIDELINES
  8. CONCLUSION
  9. REFERENCES

Management of breast cancer has improved substantially over the last two decades. Clinical experience with existing treatment in the Asia–Pacific region is limited and variable due to the small number of breast cancer trials conducted in the region. Emerging data indicate that disease patterns, efficacy and toxicities of various treatment regimens differ between Asia–Pacific women and women in the West. Thus, to optimize breast cancer treatment in Asia–Pacific women, there is an urgent need to increase clinical trials and breast cancer registries in the Asia–Pacific region. Evidence-based care guidelines, based on the consensus of treatment centers and each country's unique issues, are also an important step toward improving outcomes. These measures would facilitate to establish the best choice of drugs, optimal doses and optimal schedules for treating women with breast cancer in the Asia–Pacific region.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MANAGEMENT OF METASTATIC BREAST CANCER
  5. CLINICAL EXPERIENCE IN ASIA–PACIFIC REGION
  6. CLINICAL TRIALS IN ASIA–PACIFIC POPULATIONS
  7. NEED FOR ASIA–PACIFIC TREATMENT GUIDELINES
  8. CONCLUSION
  9. REFERENCES