On January 15 and 16 Breast Cancer Now hosted the UK’s first Interdisciplinary Breast Cancer Symposium in Manchester, bringing together the brightest minds in the field of breast cancer to make faster progress for patients.
Chaired by Breast Cancer Now scientist Professor Mitch Dowsett, the event emphasised the importance of collaboration between professionals from many disciplines in understanding breast cancer, finding the best ways to prevent and treat it, as well as improving the lives of those living with the disease.
Over two days, talks ranged from new approaches to treatment, understanding crucial differences between subtypes of breast cancer, tackling the overtreatment of DCIS, as well as ensuring those affected by breast cancer are enabled to take an active role in decisions about their care and treatment.
Treating secondary breast cancer
When breast cancer spreads to other parts of the body, known as secondary breast cancer, it can often be managed with current treatment options for a number of years, but sadly it cannot be cured. The treatment of secondary breast cancer was therefore an important strand of the conference programme.
Dr Aleix Prat, from the Hospital Clinic of Barcelona, Spain, talked about the difficulties in predicting outcomes in secondary breast cancer. There are a number of potential biomarkers that could help us to select the best treatments for each cancer, but none of them are perfect and carry enough predictive value.
Looking at intrinsic cancer subtypes, like luminal, HER2 enriched or basal-like, could help us select drugs, but there is some evidence to suggest that some intrinsic subtypes could change in tumours that have spread. The best approach for cancer classification could be putting together all the information we can gather about cancer: clinical data, genetics, how active certain genes are in cancer cells, but that may be very difficult to combine into one predictive model. Dr Prat discussed some recent and ongoing clinical trials, showing that some biomarkers can suggest how effective different drugs will be, so we are making steps in the right direction.
Dr Richard Baird presented news from the RADICAL trial in secondary oestrogen receptor (ER) positive breast cancer. The trial is specifically looking at postmenopausal women whose cancer progressed despite being treated with anti-hormone therapy. The researchers want to see if an experimental drug called AZD4547 can be combined with anti-hormone therapy drugs anastrozole or letrozole to make them effective again, so that tumours begin to shrink. AZD4547 specifically blocks a protein called FGFR1 that helps cancer cells grow, and researchers think that FGFR1 may be responsible for the development of treatment resistance. The researchers observed that AZD4547 is generally safe to use, although it did have some specific side effects. The combination of AZD4547 was effective in a subset of patients, so now they want to understand why those patients responded and if there is a biomarker which can help to identify those patients in the future.
Triple negative breast cancer
Breast Cancer Now scientist Professor Andrew Tutt gave an overview of clinical trials testing new approaches to treat triple negative breast cancer, which can be more aggressive and harder to treat than other forms of the disease. Most of these trials are combining different types of drugs, for example the LOTUS trial has recently demonstrated the promise of combining an AKT inhibitor (ipatasertib) with paclitaxel chemotherapy to treat patients with metastatic triple-negative breast cancer. AKT is a protein that helps cancer cells to grow, and research has shown that blocking AKT could be an effective way to treat cancer. A gene called PIK3CA has an important relationship with AKT, and the ongoing PAKT trial of another AKT inhibitor (AZD5363) aims to find out whether patients whose tumours have mutations in this gene benefit more from AKT inhibitors.
Next we heard from Dr Charles Perou discussing approaches that could help us in developing precision medicine for triple negative breast cancer. Dr Perou and his colleagues demonstrated that breast cancers can be classified into at least five molecular subtypes. He argued that when triple negative breast cancer is divided into these molecular subtypes, it doesn’t look like such a hard to treat disease anymore. But we still need more research to find the best treatments for each subtype.
In the same session Dr Jelmar Quist from King’s College London presented his work which has shown that the HORMAD1 protein contributes to the ability of triple negative breast cancer to rapidly accumulate changes in its genetic information. Around 50% of triple negative breast cancers seem to make this protein, and the researchers investigated what other changes are likely to happen in these cancer cells. This analysis suggested that breast cancers with high levels of HORMAD1 may be more susceptible to drugs disrupting the repair of damaged DNA in the cancer cell and the researchers are planning to investigate this exciting possibility further.
Dr Rachael Natrajan, who leads the Functional Genomics team at the Breast Cancer Now Research Centre, discussed the importance of another protein, called CREBBP, in triple negative breast cancer. Decreased levels of this protein in certain subtypes of triple negative breast cancer may be linked to poorer outcomes. By looking in detail at how cancer cells with low levels of CREBBP behave, researchers noticed that they may be sensitive to CDK4/6 inhibitor drugs, like palbociclib.
What can we do about drug resistance?
As well as searching for new drug targets, finding ways to stop tumours becoming resistant to drugs is a big challenge in breast cancer research.
Professor Stephen Johnston from The Royal Marsden talked about approaches to managing oestrogen receptor (ER) positive breast cancer, which accounts for around eight out of ten breast cancer cases. There are good anti-hormone treatment options available for this form of the disease, but over time tumours can become resistant to these drugs. Being able to predict if women are likely to develop drug resistance will be the key to managing the disease, and combination therapy could be the answer to successfully treating those who are likely to develop resistance. Professor Johnston gave an overview of clinical trials looking at the effectiveness of CDK4/6 inhibitor drugs in ER positive breast cancer, and combinations of CDK4/6 inhibitors with anti-hormone therapies. He believes that this kind of combination therapy could allow patients who develop secondary breast cancer to delay - if not avoid - chemotherapy. This approach could improve the quality of life of breast cancer patients and the key will be identifying which drugs are the most suitable for which patients.
Breast Cancer Now scientist and trustee Professor Adrian Harris discussed the molecular processes which cause breast cancer to become more aggressive. He stressed that looking at the early response to drugs is very important, as changes in the primary tumour can occur as early as two weeks into treatment. Treatment can also alter healthy cells surrounding the tumour, and we will need to learn how to take this into account when deciding on the best way to tailor and monitor each patient’s treatment plan.
Are we ready to use immunotherapy to fight breast cancer?
Immunotherapy is already used to treat some other types of cancer, but for breast cancer it is still in experimental stages. With promising results being reported from early stage trials, doctors and researchers are beginning to think about what it would mean to bring immunotherapy into breast cancer clinics.
Professor Peter Schmid from Bart’s Cancer Institute shared his thoughts on how immunotherapy could be used in breast cancer. There are two requirements for immunotherapy to work successfully: an active immune system, and a target the immune system can recognise. Before we can start using immunotherapy to treat breast cancer, we need to understand better how we can select people who would benefit from it. Looking at the number of immune cells infiltrating the tumour may be one such approach. In the first instance immunotherapy for breast cancer is most likely to be used in combination with chemotherapy, and other approaches may arise combining immunotherapy with new targeted therapies.
Professor Schmid’s thoughts were also shared by Dr Mark Harries, a Consultant Medical Oncologist at Guy's & St Thomas' Hospitals NHS Foundation Trust. He shared his experience of using immunotherapy to treat melanoma patients, and highlighted what changes may need to happen in breast cancer clinics when immunotherapies arrive. Dr Harries stressed how important it is to understand side effects, or immunotoxicities, that may result from the use of immunotherapies. If immunotherapy is combined with chemotherapy, it may be harder to distinguish which treatment is causing side effects, but the side effects from immunotherapies need to be taken seriously and treated quickly. However, if a person is showing some side effects from immunotherapy it could also mean that their immune system is successfully activated and is able to destroy cancer cells. Dr Harries believes it is possible to successfully address these side effects without decreasing the effectiveness of the immunotherapy. Doctors also need to be aware that in response to immunotherapy a tumour may initially look bigger due to immune cells infiltrating the tumour, and it may only visibly shrink later once the immune cells have had time to carry out their attack. But learning from other cancers where immunotherapy is already used in the clinic, healthcare professionals could be quickly upskilled to be able to deliver the best possible care and treatments for breast cancer patients.