Fatima Cardoso honoured with award

Doctor Fatima Cardoso awarded

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The 17th St. Gallen International Breast Cancer Conference will take place virtually from 17 to 21 March 2021. Held every two years, the congress brings together breast cancer experts from all around the world, and the consensus recommendations on the optimal treatment of early breast cancer are highly respected.

For the full programme of the conference, or for registration, click here: www.sg-bcc.org

In view of the conference, BIG interviewed Professor Beat Thürlimann, Dr Fatima Cardoso en Professor David Cameron.

Prof Beat Thürlimann talked about the establishment of the conference, its early days, its evolution and the legacy of Professor Aron Goldhirsch, Scientific Co-Chair of the St. Gallen conference for about 30 years and one of the main drivers behind the conference and the consensus. Prof Thürlimann’s interview has been published on BIG’s website on Wednesday 10 March and can be found here.

On Thursday 18 March 2021, Dr Fatima Cardoso will be honoured with the ESO Umberto Veronesi Memorial Award and will give an Award Lecture on de-escalation of early breast cancer therapy and Umberto Veronesi’s legacy. In the interview BIG had with her, which can be found below, she talks about the progress we are seeing in the field of de-escalation of early breast cancer therapy, the importance of collaboration and the advantages of a global network such as BIG.

On Saturday 20 March 2021, Prof David Cameron will give a lecture to honour the memory of Professor Aron Goldhirsch. Ahead of the conference, BIG had the pleasure to ask him a few questions about adjuvant therapies and the role Aron had in the evolution of adjuvant therapies across time, and in the evolution of academic research. Prof Cameron’s interview will be posted on the BIG website on Monday 15 March.

So watch this space, but in the meantime, enjoy reading the interview with Dr Fatima Cardoso.

Fatima Cardoso honoured with ESO Umberto Veronesi Memorial Award

Interview with Dr Fatima Cardoso on de-escalation of breast cancer treatment, Umberto Veronesi’s legacy.

Dr Fatima Cardoso, Director of the Breast Unit at the Champalimaud Cancer Center/Champalimaud Foundation (Lisbon, Portugal), is this year’s recipient of the ESO Umberto Veronesi Memorial Award, established in 2017 by the European School of Oncology to honour the memory of its founder. This award aims at recognising a physician’s leading role in advancing science and care of breast cancer patients. We asked her a few questions about her presentation on the topic of de-escalation of early breast cancer therapy [1].


What is Umberto Veronesi’s main contribution to the de-escalation of breast cancer therapies?

Umberto Veronesi’s motto was “from the maximum tolerated to the minimum necessary”. Back in the 1970s-80s, this new notion that we could treat as well as we were doing at the time, while being less aggressive, completely changed the mentalities and had an impact on all breast cancer specialties, including surgery, medical oncology and radiotherapy.

Umberto Veronesi and Bernard Fisher in the US are considered the “fathers” of breast conservative surgery, both at the level of the breast and the axilla. This had a great impact on patients’ quality of life. Veronesi’s contributions are crucial for all fields of breast cancer.

But his main contribution and legacy is undoubtedly his motto.

What progress have we seen in the field of de-escalation of early breast cancer therapy? Are these practice-changing?

I think that the best word is not really “de-escalation” but rather “optimisation”; it’s not always about providing less treatment, but optimising treatment based on several characteristics of the disease and the patient.

In the early breast cancer setting, there are various examples of de-escalation trials that have been practice-changing.

De MINDACT study (EORTC 10041/ BIG 3-04) is a typical example of treatment de-escalation. In this study we decreased the use of chemotherapy through the help of a genomic signature, the MammaPrint® test. This study has been practice-changing, since it showed that patients considered as high-risk of cancer recurrence based on traditional factors, but identified as low risk  by the MammaPrint test and treated with endocrine therapy alone (without chemotherapy), still had very good outcomes at 8 years of follow-up. Particularly for post-menopausal women, we see no clinically meaningful benefit from chemotherapy and, therefore, it can be safely omitted.

Another example is the phase II APT [2] trial, which evaluated de-escalation strategies in women with small, node-negative HER2-positive breast cancer. Sara M. Tolaney [3] and her team evaluated a chemotherapy backbone of adjuvant paclitaxel in combination with trastuzumab and found a 7-year disease-free survival rate (DFS) of 93%. Although this regimen is not adequate for all breast cancer patients, it allows for de-escalation of both a type of chemotherapy and a type of anti-HER2 therapy for “low risk” HER2-positive cases.

I think it’s important to emphasise that the notion of de-escalation should not be limited to the treatment of early breast cancer. We are seeing a shift in mentalities also in the metastatic setting. While the old way of thinking is that, since metastatic disease is incurable, you have to give everything and as much as you can in the hope that you can somehow control the disease and prolong the life of the patient. Doctors and researchers now understand the need to optimise treatments according to the characteristics of the disease and of each individual patient.

How have academic cooperative groups contributed to this process in the past and how can a network like BIG continue to contribute?

MINDACT was a great example of academic collaboration that led to practice-changing results and impacted the lives of many patients with early breast cancer.

For the future, I think that we, investigators, need to discuss with statisticians about how to run these de-escalations trials in an appropriate way that provides the level of evidence that we need, but without taking so many years as MINDACT did, for example (about 15 years).

We need to start changing mentalities in drug development itself, in terms of doses and in terms of trial design.

What we typically do is find the maximum tolerated dose. This traditionally comes from chemotherapy development. The problem is that we keep on trying to give the maximum tolerated dose even with targeted agents. But these agents were developed to hit a certain target and the efficacy is linked to “hitting the target”. We should therefore be looking for the minimum dose required, sometimes called “minimum biological effective dose”, to hit the target. This would allow us to retain efficacy and greatly decrease toxicity.

We need to start changing this from the preclinical stage up until the way phase I and then phase III trials are run. As academic groups, I believe that we need to pay attention to that, particularly in the field of targeted and biological therapies.

From my perspective, to run effective de-escalation studies, we also need innovative trial designs, and this must be done in close collaboration with regulators and pharmaceutical companies. These studies have to be statistically sound and accurate, but they can’t be run as non-inferiority trials, which demand a huge patient population. The same happened in the field of biosimilars, and a new methodology was developed and is approved by regulators. I strongly support the development of an equally effective methodology, approved by regulators, for de-escalation trials as well as for trials that aim at approving a new drug formulation or the use of lower (but similarly effective) doses.

I think that an academic network like BIG has the potential to play a key role here, to help change mentalities from the beginning of drug development, and to raise a voice in the discussions with pharmaceutical companies and regulators.

The academic community took a long time to pay attention to metastatic breast cancer. There are now different research programmes dedicated to the metastatic disease, such as AURORA (BIG 14-01), but the majority of studies run in this setting are still pharma driven and that leaves a lot of important questions unanswered for the patients.

Because metastatic breast cancer clearly has fewer patients (about 1/3 compared to 2/3 of patients with early breast cancer), international cooperation between academic groups is crucial to run trials in the metastatic setting that may not have commercial interests but tackle questions that really matter to patients.

[1] Thursday, 18 March 2021, 12.00-12.30 (CET). Award Lecture by the ESO Umberto Veronesi Memorial Award Winner Fatima Cardoso (Portugal): De-escalation of early breast cancer therapy: Umberto Veronesi’s legacy. Introduction by Franco Cavalli (Switzerland).
[2] Barroso-Sousa R., Barry W.T., Guo H. et al. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Annals of Oncology 30: 575–581, 2019. doi:10.1093/annonc/mdz047. Published online 7 February 2019.
[3] Tolaney SM, Guo H, Pernas S et al. Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer. DOI: 10.1200/JCO.19.00066 Journal of Clinical Oncology 37, no. 22 (August 01, 2019) 1868-1875.

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