Updates and advancements in breast cancer care

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Reference: August 2025 | Issue 8 | Vol 11 | Page 18

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As one of the most common malignancies worldwide, breast cancer has a substantial effect on the Irish healthcare system. It is an area of strong research focus, driving constant advancements and improvements in understanding, prevention, and treatment, all of which have an impact on breast cancer care in Ireland.

Trends

The World Health Organisation (WHO) launched the Global Breast Cancer Initiative (GBCI) in 2021, with a goal of reducing the annual mortality from breast cancer by 2.5 per cent.¹ A 2025 Nature Medicine article by Kim et al assessed breast cancer data from different global regions and countries in the context of the WHO’s GBCI goal.² The authors found that breast cancer was the first or second most commonly diagnosed cancer in 183 of 185 countries, including Ireland. Furthermore, breast cancer was among the top two causes of cancer-related death in 169 countries, again including Ireland.

In terms of incidence, Irish cohorts showed stability over the 10-year period 2008-2017, with an estimated annual percentage change of -0.32 per cent for all age groups. Ireland also showed a decrease in breast cancer mortality of -2.206 per cent, which is extremely close to achieving the GBCI goal of -2.5 per cent.

Only seven countries in this analysis have achieved the GBCI goal, namely Malta, Denmark, Belgium, Switzerland, Lithuania, the Netherlands, and Slovenia. Interestingly, these are all countries in the European region with a very high human development index (HDI) score.

Despite improvements in countries such as Ireland, which are close to reaching the GCBI goal, these successes are in the minority of countries. The study ultimately estimates global increases of 38 per cent for new breast cancer cases and 68 per cent for breast cancer-related deaths.

The authors point to evidence that addressing alcohol intake, obesity, and physical inactivity can reduce breast cancer occurrence in high-income countries. They also note that screening initiatives, such as BreastCheck in Ireland, are essential for early-stage diagnosis and the lack of such programmes may attribute to high mortality rates in lower HDI countries.

A limitation of this study is that the data analysed is from 2008-2017. Such analyses of large databases must be conducted retrospectively. However, the data in this study does not include recent factors that may influence cancer trends, in particular the Covid-19 pandemic and recent approvals of new breast cancer therapies.

Interestingly, the National Cancer Registry Ireland (NCRI) statistics on breast cancer indicate a decline in incidence in the years 2019-2021 which is directly attributed to the Covid-19 pandemic. As a result, there are significant concerns that many “missed” cancers may be diagnosed at a later date, requiring more complex treatments and conferring poorer survival outcomes.³

Diagnosis

Early detection remains the cornerstone of effective breast cancer management. Mammography continues to be the gold standard for routine screening, exemplified by Ireland’s free national screening service BreastCheck. Running for 25 years, BreastCheck has played a significant role in increasing early-stage diagnosis and lowering cancer-related mortality among women within screening age eligibility.^4,5

Diagnosis is evolving rapidly with technological advances. In late 2024, BreastCheck introduced a modernised electronic database system, in line with the HSE’s Digital Health Strategy, to streamline screening processes, and allow the BreastCheck team increased capacity to focus on patient care.

The advent of artificial intelligence-based computer-aided detection (AI-CAD) has been hailed as the future of cancer diagnostic imaging. A recent study of 24,543 women in the South Korea national breast cancer screening programme found that cancer detection rates were significantly higher when radiologists used AI-CAD, without an associated increase in recall rates.⁶

Such developments will be of interest to Ireland’s BreastCheck, which reported an increase in recall rates between 2000 and 2019, and recommend that AI-CAD should be investigated as a method to ensure the benefits of screening are maximised and all potential harms are minimised.^7,8

Emerging trends

By measuring the expression of 21 genes, the Oncotype DX test provides a recurrence score, which predicts the likelihood of cancer recurrence, and the potential benefit of chemotherapy for a patient.⁹ Clinicians can then use this score to determine if chemotherapy is necessary for that patient, helping to avoid unnecessary overtreatment.

Ireland was one of the first countries to approve public healthcare reimbursement of the Oncotype DX test, and recent real-world analyses of Irish breast cancer patients, conducted by Browne et al and Ronan et al, evidenced the value of this testing, reporting a 58 per cent reduction in chemotherapy administration and net savings of over €4.7 million for the Irish healthcare system.^10,11

Circulating tumour DNA (ctDNA) has emerged as a useful biomarker for surveillance and minimal residual disease monitoring in several solid tumours, including breast cancer. By analysing small fragments of tumour-derived DNA found in the bloodstream, this non-invasive technique enables earlier intervention and more personalised treatment decisions. Irish oncology researchers are increasingly exploring ctDNA-based minimum residual disease (MRD) monitoring as part of clinical trials and translational research, aiming to integrate it into routine breast cancer care to both improve patient outcomes and reduce costs.^12-14

Novel therapeutics

Advancements in targeted breast cancer therapies have also been seen in recent years. In the context of hormonal receptor positive (HR+) breast cancer, clinical research has been focused on the development of orally available selective oestrogen receptor degraders (SERDs). The first approved SERD, fulvestrant, offers effective treatment for metastatic HR+ breast cancer patients after progression on earlier lines of hormonal therapy.¹⁵ Although it has been the only approved SERD for over 20 years, fulvestrant has pharmacokinetic limitations and poor bioavailability, and so must be administered by high-dose intramuscular injections.

Orally available SERDs offer a promising alternative to fulvestrant, with several candidates in clinical trials, and the approval of elacestrant in 2023.¹⁶ Trials of other orally available SERDs, camizestrant and giredestrant, are currently running, with sites in Ireland, offering positive results thus far.^17-20

It remains to be decided if these orally available therapies offer benefit over the standard-of-care hormonal therapies. Furthermore, there is a lack of research in this patient cohort on preferences and opinions in choosing monthly injections compared to an oral tablet, and the associated impact on quality of life.

Other advancements in the treatment of HR+ breast cancer include cyclin dependent kinase 4/6 inhibitors (CDK4/6i) such as abemaciclib, palbociclib, ribociclib, which have been approved for use and reimbursement for Irish breast cancer patients.²¹ CDK4/6i are now used in combination with hormonal therapies, with the aim of preventing or overcoming hormonal therapy resistance in advanced breast cancer or in early breast cancer at high risk of recurrence.²²

Phosphoinositide 3-kinase inhibitors (PI3Ki), for example, alpelisib, are another emerging therapy class for HR+ breast cancer. Alpelisib added to fulvestrant displayed benefit in advanced breast cancer with a PIK3CA mutation, leading to approval by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).²³ However, to date, it has not been considered for patient reimbursement, following a recommendation from the National Centre for Pharmacoeconomics (NCPE).²⁴

In a similar vein, capivasertib, a first-in-class AKT inhibitor was recently approved in 2024 for the treatment of advanced HR+ breast cancer with one or more PIK3CA, AKT1 or PTEN mutations, but is awaiting full health technology assessment from the NCPE before recommendation for reimbursement in Ireland.^25,26

In HR-negative (HR-) breast cancers, antibody-drug conjugate (ADC) therapies have emerged to offer new therapeutic options. ADCs offer the benefit of delivering effective chemotherapy targeted to tumour cells, with the aim of reducing off-target effects.²⁷

Trastuzumab deruxtecan (T-DXd) is one example of such ADCs, combining a HER2 targeting antibody with a potent topoisomerase inhibitor-based chemotherapeutic payload. T-DXd has shown exceptional benefit in HER2+ and HER2-low metastatic breast cancer patients, who have progressed on prior lines of therapy and is available for Irish patients in this setting.²¹

Trials are now underway to examine the use of T-DXd as a first-line therapy for this cohort, comparing T-DXd + pertuzumab (P) vs standard-of-care taxane + trastuzumab + pertuzumab (THP), with recent updates presented at the 2025 American Society of Clinical Oncology Annual Meeting, reporting significant improvement in progression-free survival associated with the drug.²⁸

Triple-negative breast cancer (TNBC) has historically been the most challenging subtype to treat due to its lack of targetable characteristics and aggressive phenotype. Breakthroughs have been made in finding targeted therapies that offer alternatives for TNBC patients, beyond traditional chemotherapy.

The ADC sacituzumab govitecan, consisting of a Trop-2 targeting monoclonal antibody and the chemotherapeutic payload SN-38, was authorised by the EMA in 2021 and approved by the HSE for reimbursement in 2024 as monotherapy for unresectable or metastatic TNBC, following two or more prior systemic therapies.^29,30

The 2025 Irish therapeutic landscape for TNBC also includes olaparib, a PARP inhibitor now available for patients with BRCA1/2 germline mutations, as well as the immune checkpoint inhibitors atezolizumab and pembrolizumab, which are indicated for PD-L1-positive and advanced or high-risk TNBC disease.²¹

Conclusion

The treatment landscape for breast cancer is constantly evolving, with a recent emphasis on providing individualised and de-escalated treatment plans that can spare patients from overtreatment, adverse events, and a decline in quality of life. Providing more personalised treatments for breast cancer patients has become more achievable due to 1) the use of treatment decision guiding molecular diagnostics and 2) the approval of a wide repertoire of targeted breast cancer therapies.

As technologies and therapeutics improve, it is essential that Ireland remains up to date, particularly in terms of the infrastructure needed for increased molecular diagnostic testing, data sharing among cancer care stakeholders, and ensuring the availability of novel approved therapies.³¹

Best practice management now requires a multidisciplinary approach that integrates personalised risk assessment, patient-centred decision-making, and new therapeutics. Continuous updates from ongoing clinical trials and real-world evidence will further refine strategies, aiming to maximise survival while minimising toxicity and preserving quality of life for Irish breast cancer patients.