St. Gallen International Breast Cancer Conference 2023 - Day 1

Global Breast Cancer Initiative, therapy updates since SGBCC 2021, HER2+ developments

The 18^th St. Gallen International Breast Cancer Conference 2023 was held at the Austria Centre Vienna, from 15—18 March. This is the first in a series of three articles covering important highlights from this conference.

ESO Award and Global Breast Cancer Initiative

The opening sessions of this year’s St. Gallen international breast cancer (BC) conference emphasised the burden of cancer worldwide and inequalities in cancer care. Benjamin Anderson from the World Health Organization, who was the recipient of the ESO Umberto Veronesi Memorial Award 2023, introduced the Global Breast Cancer Initiative (GBCI)¹. GBCI aims to reduce breast cancer mortality by 2.5% annually, which over 20 years could save 2.5 million lives². Globally, low- and middle-income countries have the highest avoidable rates of deaths from breast cancer, with >70% occurring in women aged under 70 years².

Benjamin Anderson of the WHO was awarded the ESO Umberto Veronesi Memorial Award 2023 for work on the Global Breast Cancer Initiative

Fatima Cardoso highlighted the importance of resource-stratified guidelines³. Using the adapted ESMO Magnitude of Clinical Benefit Scale, a study found that only 11% of EMA-approved cancer medications over five years met the threshold for benefit⁴. The approval of drugs by the FDA (2006—2017) had a median gain in overall survival (OS) of 2.45 months⁵.

Few drugs provide the same survival benefit as compliance with guidelines, multidisciplinary care, experience, and quality-of-care. Surgeon and departmental experience can improve 5-yr OS by 10% and the implementation of a multidisciplinary team by around 20%. The European Society of Breast Cancer Specialists (EUSOMA) requirements and certification system aims to put the quality-of-care standard in place in every country to ensure every patient is treated within this framework⁶.

Only two-thirds of patients across Europe who should be treated with optimal radiation therapy (RT) receive it⁷ (Philip Poortmans)⁸. Implementation of findings from evidence-based studies are required to improve access to RT for patients with BC. In a study of over 12,000 patients (8 trials), hypofractionation had the same efficacy and reduced overall treatment time from the first to the last session and, therefore, should be standard. In the HERA trial⁹, delivery of an additional radiation boost to patients with HER2+ BC post-mastectomy did not show an improvement in loco-regional recurrence rates. Thus, RT boost should only be used for cases with high-risk local recurrence. The current resistance to hypofractionation is due to outdated reimbursement systems. Changes to these systems and appropriate use of existing resources would result in more cost-effective healthcare and improved clinical outcomes.

Implementing consistent standards of care and improving access to care, combined with advances in treatment efficacy, aims to reduce the burden of breast cancer worldwide

Clinical Trial Updates

Walter Weber presented an international study comparing targeted axillary dissection (TAD) and sentinel lymph node biopsy (SLNB) in early breast cancer (eBC), which showed a recurrence rate of 0.5% and 0.8%, at three years, respectively¹⁰. Compared to SLNB only, TAD allows for the removal of fewer lymph nodes; likely a relevant finding. Autologous reconstruction requires more surgery, but has fewer complications and better patient-reported outcomes (PROs) than patients with implant reconstruction. The TAXIS trial (NCT03513614) is currently investigating a tailored axillary surgery approach (TAS) where only affected lymph nodes are removed, followed by regional irradiation, avoiding surgical overtreatment. Preliminary results will be available in 2029.

Updates in systemic therapies were presented by Roisin Connolly¹¹. Updated 12-year data from the SOFT and SOFT-TEXT trials confirm the benefit of ovarian suppression in both disease-free survival (DFS) and overall survival (OS). CDK4/6 inhibitor trial data show that not all inhibitors are equal in the metastatic setting. PALLAS and PENELOPE-B (palbociclib) trial results were disappointing, with no DFS advantage and a higher discontinuation rate. However, updated results from the Monarch-E study (abemaciclib) show an ongoing and increasing improvement in DFS when added to an endocrine therapy (ET) backbone, leading the FDA to recently change the indication for abemaciclib.

Promising results were also reported from the POSITIVE trial in women (<42y), where ET was interrupted to allow for pregnancy. The primary outcome of BC-free interval was similar to the SOFT-TEXT trial. Secondary endpoints showed that 74% of women had at least one on-trial pregnancy, 64% had one live birth, and 62% could breastfeed. Pregnancy complications were similar to age-matched controls.

Updated results from the RxPONDER trial indicate no benefit of chemotherapy (CT) in postmenopausal women, with a recurrence score of under 25. Further analysis is required to determine whether the CT benefit in premenopausal women is a CT effect or CT-induced menopause.

In TNBC, there were no updates for immunotherapy. However, results from the Olympia trial have been practice-changing. High-risk ER+ TNBC, BRCA1/2 carriers received adjuvant olaparib or placebo for one year. The difference in the primary outcome of 3-year IDFS between the groups was 9%, and an observed survival advantage of 3%. Further results are awaited. In the neoadjuvant setting, data indicates the benefit of capecitabine and platinum.

According to Fabrice André, cancer has multiple clones with specific spatial distribution, which is important for predicting drug sensitivity¹². As it is now known that tumours are also full of bacteria, the role of the microbiome in drug sensitivity and the development of specific antibodies should also be considered. The involvement of the ApoBEC family of cytidine deaminases is enriched in HER2+ subtypes and is associated with a response to immunotherapy in other cancer types. Therefore, it is important to quantify residual disease. A study found that more circulating tumour cells are detectable when patients rest. These data are essential for translational research, as the timing of sample collection and, in the future, timing therapies may be necessary. Translational research has shown that BC is a complex system, and multicomponent predictors need to be developed.

References

1. Anderson B. The ESO Umberto Veronesi Memorial Award Lecture 2023: A global approach to breast cancer management. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Opening Ceremony.
2. World Health Organization. Global breast cancer initiative implementation framework: assessing, strengthening and scaling up of services for the early detection and management of breast cancer. 2023. Available at: https://www.who.int/publications/i/item/9789240065987. Accessed 20 March 2023.
3. Cardoso F. How to avoid unnecessary mastectomies – a global discussion. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Interactive Session 1.
4. Grössmann N, Del Paggio JC, Wolf S, Sullivan R, Booth CM, Rosian K, et al. Five years of EMA-approved systemic cancer therapies for solid tumours—a comparison of two thresholds for meaningful clinical benefit. European Journal of Cancer. 2017;82:66-71.
5. Douillard J-Y. ESMO Magnitude of Clinical Benefit Scale as a tool for treatment decision and prioritization: Focus on Gastro-Intestinal Cancers. https://oncologypro.esmo.org/content/download/135149/2507045/file/WORLDGI2018_75_douillard.pdf. Accessed 20 March 2023.
6. Biganzoli L, Cardoso F, Beishon M, Cameron D, Cataliotti L, Coles CE, et al. The requirements of a specialist breast centre. The Breast. 2020;51:65-84.
7. Cardoso F, Macneill F, Penault-Llorca F, Eniu A, Sardanelli F, Nordström EB, et al. Why is appropriate healthcare inaccessible for many European breast cancer patients? – The EBCC 12 manifesto. The Breast. 2021;55:128-135.
8. Poortmans P. Access to evidence based radiation therapy for patients with early breast cancer. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Session 1.
9. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659-1672.
10. Weber W. Surgery of patients with early breast cancer: Quo vadis? Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Session 1.
11. Connolly R. What’s new in systemic treatment of patients with early breast cancer. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Session 1.
12. André F. Translational research priorities for patients with early breast cancer. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Session 1.
13. Harbeck N. Current adjuvant and neoadjuvant approaches. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Session 8.
14. Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021;39(13):1448-1457.
15. Chan A, Moy B, Mansi J, Ejlertsen B, Holmes FA, Chia S, et al. Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial. Clin Breast Cancer. 2021;21(1):80-91.e87.
16. Nitz U, Gluz O, Graeser M, Christgen M, Kuemmel S, Grischke EM, et al. De-escalated neoadjuvant pertuzumab plus trastuzumab therapy with or without weekly paclitaxel in HER2-positive, hormone receptor-negative, early breast cancer (WSG-ADAPT-HER2+/HR-): survival outcomes from a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2022;23(5):625-635.
17. Piccart M. Emerging new treatments in HER2 positive breast cancer. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Session 8.
18. Colombo R, Rich JR. The therapeutic window of antibody drug conjugates: A dogma in need of revision. Cancer Cell. 2022;40(11):1255-1263.
19. Prat A. ER positive vs ER negative: tackling diversity in HER2 positive breast cancer Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Session 8.
20. Filho OM, Viale G, Stein S, Trippa L, Yardley DA, Mayer IA, et al. Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab. Cancer Discov. 2021;11(10):2474-2487.
21. González-Santiago S. Randomized Phase II trial evaluating three anti-diarrhoeal prophylaxis strategies in patients with HER2+ / HR+ early breast cancer treated with extended adjuvant neratinib (DIANER GEICAM/2018-06). Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Poster P006.
22. Bartsch R. Interim analysis of ELEANOR (n=200): a multi-national, prospective, non-interventional study (NIS) among patients with HER2+ and HR+ early breast cancer (eBC) treated with extended adjuvant neratinib. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Poster P014.
23. Harbeck N. A real-world prospective observational multi-national study in adult patients with breast cancer treated with extended adjuvant neratinib: NERLYFE study. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Poster P009.
24. Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, et al. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. N Engl J Med. 2021;385(25):2336-2347.
25. Browne IM. Real-world analysis of the clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage node positive breast cancer in Ireland. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Poster P008.
26. Antonini M. Real World Evidence of the Impact at Neoadjuvant Chemotherapy Treatment on the Prognosis of Patients with Early Breast Cancer. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Poster P131.
27. Dannehl D. Retrospective modeling of adherence to endocrine therapy in early breast cancer using real-world claims data. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Poster P010.
28. Johnston SRD, Toi M, O'Shaughnessy J, Rastogi P, Campone M, Neven P, et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24(1):77-90.
29. Hall PS. Patient Characteristics, Treatment and Long-term Outcomes from a Real-World Population of Early Breast Cancer Patients at High risk of Recurrence in Scotland. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Poster P016.
30. Hall P. Socioeconomic Outcomes With Ribociclib in Patients With HR+, HER2– Advanced Breast Cancer (ABC) in UK Real-world Settings. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Poster P084.
31. Kovacevic MM. Real-World Experience with CDK4/6 Inhibitors for Metastatic HR+/HER2− Breast Cancer at a Single Cancer Center. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Poster P082.
32. Meattini I. De-escalation of radiation therapy after primary systemic therapy in non-metastatic breast cancer: patterns of recurrence from a real-world single-centre cohort of patients. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Poster P106.
33. Canino F. Cardiac safety of pertuzumab, trastuzumab and standard chemotherapy as neoadjuvant treatment for HER2 positive breast cancer: real world data from NeoPowER trial. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Poster P120.
34. Loibl S, Chia S. If you achieve pCR after neoadjuvant, do you need adjuvant therapy? Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Debate 3.
35. Barrios C, Xu B, Gamal H, Bretel D. Global Perspective on breast cancer treatment. Presented at the St Gallen International Breast Cancer Conference 2023, 15-18 March. Vienna. Session 10.