By Pasha Yuen
Breast Cancer Facts and Figures
Breast cancer is one of the most common cancers in the UK, with approximately 56,000 new cases in women, and 400 new cases in men every year. One of the main contributing factors are genetics and family history, accounting for 15% of breast cancer cases, with BRCA1 and BRCA2 genes mutation being one of the most dominant causes that is heritable. However, with joint effort, the mortality rate of breast cancer has reduced by 41% since 1970s.
Diagnosis Breakthroughs
As mentioned in our previous blog, technological advancements in screening methods helped with an improvement in early and accurate detection, for example a 3D mammogram. This is a screening tool designed to take multiple X-rays from various angles to construct a 3D image of the breast. 3D mammograms are expected to be a more accurate diagnosis tool, especially for women with dense breast tissue, where traditional mammography alone may not be powerful enough.
Another factor for accurate diagnosis is data interpretation. Incorporation of AI into the process of breast image interpretation may help radiologists analyse images more efficiently in the future. There are several ways that AI has been proposed to help, including improving image quality by enhancement and noise cancelling, which may help to detect tumours earlier; and establishing AI algorithms to automate analysis so that routine images can be processed more quickly, allowing the radiologists to focus on trickier problems that require their expertise. (https://www.bcrf.org/blog/ai-breast-cancer-detection-screening/)
There are also advances in the blood tests we can use to determine the likely responses to treatments. The SWOG S1007 (RxPONDER) study showed that anti-Müllerian hormone (AMH) is a potential predictor for chemotherapy benefit in premenopausal patients. Results revealed a significant interaction between AMH and chemotherapy benefit. In 79% of premenopausal patients who have a AMH level of 10 pg/mL or above, Endocrine therapy (ET) with chemotherapy was beneficial when compared to ET alone (HR=0.48; 95% 0.33-0.69). In contrast, patients with AMH level less than 10 pg/mL showed a poorer response (HR=1.21; 95% 0.60-2.43).
The monarchE study suggests that circulating tumour DNA (ctDNA) could be a prognostic marker of worse outcomes. This shows that ctDNA can be a useful parameter measure for the evaluation of efficacy in future clinical trials.
Recent advances in therapies for breast cancer
In January 2024, the UK NHS announced the first targeted therapy for advanced breast cancer caused by BRCA gene mutations: Talazoparib (Talzenna). Approved by the EMA in 2019, Talazoparib is a human poly-ADP ribose polymerase inhibitor (PARPi), which is used in patients with HER2-negative breast cancer with BRCA mutation, that could be either locally advanced or metastatic. Talazoparib blocks the DNA damage repair activity by PARP in cancer cells, ultimately leading to cancer cell death. Talazoparib was found to be effective in terms of progression-free survival, when compared to standard chemotherapy, with superior patient-reported outcomes (Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation – PubMed (nih.gov)).
Following the ASCO Annual Meeting back in July, some pieces of exciting news were mentioned regarding recent successes in breast cancer treatments. The following are the highlights from the meeting:
- Metastatic Breast Cancer
- Positive results seen in DESTINY-Breast06, demonstrating that trastuzumab significantly improved progression-free survival (PFS) to 13.2 months, when compared to the chemotherapy arm, with a PFS of 8.1 months in ER+ HER2-low metastatic breast cancer.
- The MONARCH study met its primary endpoint, so the PostMONARCH study was initiated to follow up on whether continuing CDK4/6 inhibitors (abemaciclib) with fulvestrant after progression in ER+ metastatic breast cancer showed any benefits. The results showed modest benefits, with PFS rates at 6 months of 50% vs 37% when comparing the abemaciclib and placebo arms. This is the first study that shows a statistically positive result of continuing CDK4/6 inhibition post-progression.
- The TBCRC048 study investigated the use of PARPi (olaparib) in breast cancer (excluding HER-negative cancer or germline BRAC1/2 carriers). Results showed confirmed responses of ORR in patient with germline PALB2 or somatic BRCA1/2 mutations, with an overall response rate of 75% and 36.7%, respectively.
There are also other ongoing clinical trials targeting different types of mutation with various agents, including:
- TQB2102-III-01, a Phase III randomised study in HER2-low, HR+ metastatic breast cancer to evaluate the efficacy and safety of TQB2102 injection for chemotherapy-naïve patients. TQB2102 is an anti-HER2 monoclonal antibody that inhibits DNA replication in cancer cells, triggering cell cycle arrest and ultimately apoptosis.
- GS-US-598-6168, a Phase III open-label study in HR+/HER- metastatic breast cancer to compare the effect of Sacituzumab Govitecan and Treatment of Physician’s Choice on PFS. Sacituzumab Govitecan is an antibody-drug conjugate, which the monoclonal antibody, Sacituzumab, targets the Trophoblast cell surface antigen-2 (TROP2) protein. After binding to the protein, Sacituzumab releases the chemotherapy agent, Govitecan, for its cytotoxicity effect (Sacituzumab govitecan (Trodelvy) | Cancer Research UK).
- CAPItrue, a Phase IIIb, two-cohort, single arm study in HR+/HER- advanced breast cancer following recurrence or progression on or after treatment with endocrine therapy. This study aims to investigate the efficacy of Capivasertib with Fulvestrant by assessing time to first subsequent treatment. Capivasertib is a AKT inhibitor, targeting the PI3K/AKT/PTEN pathway which is often dysregulated in cancer and drives tumorigenesis.
Breast cancer remains as one of the most common causes of cancer death. However, these advances in either diagnosis tools or treatment options are a step in the right direction towards lowering the mortality rates. According to Breast Cancer UK, the mortality rate of breast cancer is projected to be reduced by 13% between 2023 and 2040, and Pharmora is pleased to continue to support these global efforts with the assured services provided by our medical department.
Ref:
Advances in Breast Cancer Research – NCI
Breast Cancer: An Overview of Current Therapeutic Strategies, Challenge, and Perspectives – PMC (nih.gov)
Facts and figures | Breast Cancer UK
