The 18th St.Gallen International Breast Cancer Conference (SG-BCC 2023) was held in Vienna, the “City of Music,” from March 15 to 18, 2023. Academician Binghe Xu from the Cancer Hospital of the Chinese Academy of Medical Sciences delivered a presentation titled “Breast Cancer Treatment and Research – An Asian Perspective” during the “Session 10: Global Perspective on Breast Cancer Treatment.” After his presentation, Academician Binghe Xu had an interview with Oncology Frontier to discuss related content.
Oncology Frontier: As a Chinese expert, entering the St.Gallen conference after a long absence, what are your feelings?
Academician Binghe Xu: This is the first in-person international conference I have attended after the COVID-19 pandemic, and it’s also a global event that the breast cancer community has been anticipating for two years. My impression is that the majority of international experts in the field of breast cancer have attended this conference, and it has attracted numerous other professionals. Although there are only a few Chinese experts in attendance, they are all members of the organizing committee. So, I believe this conference is proceeding as planned and appears to be very successful. I also hope that through the expert presentations and discussions over these days, we can achieve success in reaching a consensus in the final vote.
Oncology Frontier：At this conference, you, as the representative from Asia, presented the outlook on breast cancer treatment in Asia. Could you briefly introduce the current situation and prospects of breast cancer treatment in Asia from your perspective?
Academician Binghe Xu: Overall, Asian breast cancer patients differ from their global counterparts in terms of incidence, age of onset, disease characteristics, and management. First, Asian breast cancer patients tend to be relatively younger, and the incidence of breast cancer in Asia continues to rise. The peak incidence of breast cancer in Asia occurs between the ages of 45 and 49, whereas in the United States, the peak incidence is around 70 years old.
Second, the biological behavior of breast cancer in Asia differs somewhat from other regions, especially when compared to Western countries. These differences manifest in the frequency of TP53 gene mutations, HER2 expression, and patient response and safety to treatments.
Third, the differences in biological behavior and incidence may lead to variations in the management of Asian breast cancer patients compared to Western countries. This includes differences in imaging diagnosis, clinical treatment, and drug safety.
In general, international multicenter clinical studies currently include relatively few Asian populations, which may limit their ability to fully reflect the safety and efficacy of drugs for Asian populations. Therefore, we hope that in future international multicenter clinical studies, more Asian countries and more Asian breast cancer patients will participate to enhance the scientific validity and applicability of the research, fully reflecting the global landscape of breast cancer treatment.
Oncology Frontier: One distinctive feature of SGBCC is the formation of consensus through expert voting. How do you view this approach?Live Cov
Academician Binghe Xu: Currently, many expert consensuses are developed through voting. The consensus voting involves experts from various fields such as surgery, internal medicine, radiology, imaging, pathology, and even some patient representatives. It reflects the basic opinions of experts in various fields during the diagnosis and treatment of breast cancer. If the majority of experts agree on a voting issue, it demonstrates that the related treatment is generally acceptable. However, there are also highly controversial issues in voting that require further discussion. If consensus cannot be reached through discussion, those issues should not be included in the consensus.
Expert consensus reached through discussion and voting has important implications for future clinical trials and guideline development. Experts in the field identify the need for consensus based on clinical practice issues, conduct systematic evaluations of relevant evidence, consider the pros and cons, and reach a consensus or provide the most appropriate recommendations through discussion. This results in authoritative medical documents that help healthcare professionals make important clinical diagnostic and treatment decisions.
On the morning of March 18, local time, Academician Binghe Xu from the Cancer Hospital of the Chinese Academy of Medical Sciences delivered a lecture titled “Breast Cancer Treatment and Research – An Asian Perspective” during the “Session 10: Global Perspective on Breast Cancer Treatment.” “Oncology Frontier” has provided a summary.
Characteristics of Asian Breast Cancer Patients
▌Continuous Increase in Breast Cancer Incidence
Over the past few decades, breast cancer incidence in Asia has been on the rise. This trend may reflect the combined effects of population factors related to social and economic development.
▌Higher Proportion of Young Breast Cancer Patients in Asia
Meanwhile, the age of onset of breast cancer patients in Asia is earlier compared to Western countries. Data shows that in Western countries, about 20% of breast cancer patients are diagnosed under the age of 50, while in Asian countries, over 40% of breast cancer patients are diagnosed under the age of 50. In East Asia (China, Hong Kong, Taiwan, Japan, and Korea), the peak incidence of breast cancer is between 45 and 49 years old, while in the United States, the peak incidence is around 70 years old.
▌Tumor Characteristics of Asian Breast Cancer
Higher proportion of HER2-enriched molecular subtype of breast cancer
Increased frequency of TP53 mutations
More active immune microenvironment
Management of Asian Breast Cancer Patients
▌Considerations for Imaging Examinations and Patient Monitoring:
Mammography: The high breast density in East Asian women limits the sensitivity and specificity of this method.
Ultrasound: Widely used as a supplementary screening tool in Asian countries. Ultrasound has higher sensitivity for screening high-risk women and is superior to mammography.
MRI: Not widely used in Asian countries among average-risk women due to cost and a higher rate of false positives.
▌Chemotherapy Efficacy
Based on retrospective comparisons of the use of paclitaxel and capecitabine in East Asia and globally, the chemotherapy efficacy in Asians is generally comparable to that in Caucasians. East Asian populations have slightly higher response rates, 12-month overall survival rates, and progression-free survival rates compared to the global population.
▌Consistency of Asian Population with Global Environment
T-DXd (trastuzumab deruxtecan) benefits Asian patients with HER2+ breast cancer. In the DESTINY-Breast03 study, 309 participants (59%) were from Asian countries/regions (Korea, Japan, mainland China, Taiwan of China, and Hong Kong of China). In the Asian subgroup, T-DXd demonstrated clinically significant progression-free survival (PFS) benefits and safety compared to T-DM1, consistent with results observed in the overall population. Rates of drug-related interstitial lung disease were similar between Asian and non-Asian populations.
Efficacy and Safety Differences
▌CDK4/6 Inhibitors Show Greater Benefit in Asian Breast Cancer Patients
Racial differences can affect the effectiveness of first-line treatment in advanced breast cancer. In Chinese patients with HR+/HER2- advanced breast cancer who had previously failed first-line treatment, palbociclib reduced the relative risk of disease progression by 58%.
▌HER2 TKIs Demonstrate Better Efficacy in Asian Populations
A summary analysis of seven studies observed improvements in objective response rate (ORR), clinical benefit rate (CBR), and PFS among Asian patients treated with neratinib compared to non-Asian patients. These outcomes may be due to longer treatment duration, differences in previous treatment regimens, and variations in the underlying genetics or biology of breast cancer in Asian populations.
▌Tamoxifen Performs Poorly in Asian Populations Due to CYP2D6 Variants; Torimifen May Be Better
CYP2D6 plays a crucial role in the metabolism of tamoxifen, and the CYP2D6*10 variant is associated with reduced enzyme activity and lower plasma concentrations of active metabolites of tamoxifen. CYP2D6*10 is more common in Asian populations, which reduces the efficacy of tamoxifen treatment. Torimifen may potentially achieve better clinical outcomes than tamoxifen in Chinese breast cancer patients receiving adjuvant endocrine therapy, but this result requires confirmation in large-scale prospective clinical trials.
▌Chemotherapy – Different Safety Profiles in Asian Populations
Docetaxel: Asian patients receiving chemotherapy have a higher incidence of neutropenia compared to non-Asian patients, despite lower chemotherapy doses in some Asian countries.
Fluorouracil: Asian patients metabolize capecitabine faster than Caucasians, making them more likely to tolerate higher doses of capecitabine without compromising efficacy. The risk of grade 3 and 4 gastrointestinal toxicity during fluorouracil treatment in American patients is 3.5 times higher than that in Asian patients.
▌Endocrine Therapy – Different Safety Profiles in Different Populations
Fulvestrant: Asian patients have a lower incidence of adverse events such as fatigue, diarrhea, and inflammation. This difference may be related to pharmacokinetics, treatment compliance, and differences in menopausal status among different ethnicities. Given the heterogeneity in non-Caucasian populations and the limited number of Asian patients, these results need to be confirmed in other aromatase inhibitor trials.
▌Targeted Therapy – Different Safety Profiles in Different Populations
Neratinib: Neutropenia and leukopenia are more common in Asian patients.
Pertuzumab: Neutropenia and oral mucositis are more common in Asian patients.
Abemaciclib: Adverse events are more common in East Asian patients, including neutropenia, leukopenia, alopecia, and increased ALT and AST levels.
Conclusion
Some unique characteristics of Asians imply specific medical needs and treatment approaches. Currently, more Asian data/products are emerging to meet the treatment needs of Asian populations. Tumor genomics, patient pharmacogenomics, and genotype-guided drug research may contribute to individualized treatment that balances efficacy and safety. Inclusion of more Asians in various clinical trials will be a crucial step in meeting the unmet medical needs of Asian populations.
Academician of the Chinese Academy of Engineering, Member of the Chinese Academy of Medical Sciences
TAG: Interview, Commentary, SGBCC 2023, Breast Cancer
