METUPUK (Metastatic Exchange To Unleash Power) attended the 2024 United Kingdom’s Interdisciplinary Breast Cancer Symposium in Birmingham, hosted by Breast Cancer Now and supported by numerous partners.

It was a fantastic opportunity for us to be together, to meet oncologists, research scientists and patient advocates, and to speak with drug companies. METUPUK had a charity table in the main hall where we showcased much of the work that we
do as a charity.

UK Interdisciplinary Breast Cancer Symposium Partners 2024
This review outlines a brief summary of some of the lectures that Kirstin Spencer attended. Kirstin is a member of our drug access team, and leads the SMC patient submissions for METUPUK.

The Basic/Translational Breast Cancer Review of the Year was presented by Rob Clarke (University of Manchester) and looked at four papers:

1. Single cell atlas of the human breast (Kumar et al., Nature. 2023): This study
identified the various cell types which make up human breast tissue, highlighting the
diversity among epithelial cells (which line body surfaces) and stromal cells (connective tissue cells supporting structure). They found two main features in
epithelial cells: hormone sensitivity and the ability to develop into secretory cells.
They also identified 10 types of cells related to the origins of different breast cancer
types (ER+, HER2+, and triple-negative).

2. Clonal Evolution during breast development presages (warns of) cancer (Nishimura et al., Nature. 2023): Researchers discovered that specific chromosomal changes could predict breast cancer risk as early as age 11-12, in both premenopausal and postmenopausal women. This change is linked to a specific breast cancer subtype, raising questions about the evolution of cancer from normal cells.

3. Classification of Four ER+ / HER2- luminal breast cancer subtypes (Jin et al., Nature Genetics. 2023): This study classified four subtypes of ER+/HER2- luminal breast cancer based on a protein complex mutation common in cancers. The subtypes differ in how they’re regulated (by oestrogen, immune system, or stromal cells) and their response to therapies, suggesting the need to explore new treatment options for these specific cancer subtypes.

4. The metastatic spread of breast cancer accelerates during sleep (Diamantopoulou et al., Nature. 2022): This research found fewer circulating tumour cells were detected in breast cancer patients during active hours and more during rest. This raises questions about whether the timing of cancer treatments could be optimised based on the body’s circadian rhythm for better effectiveness.

The Plenary Lecture was on the Clinical implications of late recurrence and dormancy and given by Dan Hayes (University of Michigan, Ann Arbor, USA).
It was shown that ER-positive breast cancer patients who stopped endocrine therapy after 5 years without recurrence show varying risks of distant late recurrence based on lymph node involvement and tumour size.

For T2 tumours (2cm-5cm) risk 5-20 years post primary diagnosis is
• 4-9 positive nodes 41%
• 1-3 positive nodes 26%
• 0 positive nodes 19%

Despite advancements reducing these rates, recurrence risk remains above zero even after 20-30 years. However, 80-90% of those without recurrence after 5 years of therapy are unlikely to die from metastatic breast cancer. The necessity of extending endocrine therapy beyond 5 years remains debated, especially for node-negative cases. The session on genetic testing and optimising patient care examined how expanding relative risk is considered. In 2003, Santen looked at potential risk factors for breast cancer and it was found that breast density had the highest relative risk followed by blood oestrogen levels, bone density, late first birth, weight gain, late menopause, waist hip ratio, hormone replacement therapy (oestrogen and progesterone), menstruation starting before the age of 12, exercise and

Genomic analysis via genetic testing has broadened how the disease can be analysed. It was discussed that it may be better to offer different gene set analysis for different clinical scenarios rather than a one size fits all panel. Family history plays a part too. There are currently more than 300 known genetic variants that can increase the risk of breast cancer by between 8-40%.

As an invasive lobular metastatic breast cancer patient myself, some precision targeting in any area of our understudied disease would be welcome.

The plenary lecture on ER+ HER2- metastatic breast cancer by Stephen Johnston from the Royal Marsden Hospital, London, explored the potential of cycling through CDK 4/6 inhibitors after disease progression, showcased by the MAINTAIN Phase 2, post MONARCH, and EMBER-3 trials. He highlighted that endocrine resistance is often linked to genetic mutations or cellular pathway interactions, emphasizing that drug-induced mutations can render cancer ‘incurable.’

Johnston also reviewed significant trials: BOLERO-2 demonstrated everolimus’ effect on progression-free survival but not overall survival; SOLAR-1 showed alpelisib and fulvestrant significantly outperform fulvestrant alone in endocrine-resistant cases; and the BYLieve trial compared alpelisib with fulvestrant versus letrozole.

PI3Ka was shown to be an important target. Progress in inhibiting PI3K is coming and drugs are already in trials. A drug which has shown particular potential is the PI3Ka inhibitor and degrader Inavalosib Certainly, all this this heralds a dynamic time ahead for ER positive metastatic breast cancer treatment. There is good research happening and exciting ways of targeting this expansive disease. It seems the disease is particularly challenging as no two people are the same, no two diseases are exactly the same. I remember my oncologist telling me he had treated thousands
of women over his career, and he has yet to see two diseases that are the same. However, common ground is being found and targeted.

One of the ‘takeaways’ given to me from discussions with Lilly Oncology who make Verzenio (abemaciclib) is how important it is that if patients suffer substantial side effects from this drug (so their bodies are obviously sensitive to it), rather than give up on it or move to a different drug losing this line of treatment, they can talk to their oncologists about reducing the dose without reducing the efficacy of the drug. This was explored in the MonarchE phase 3 Trial.

What we need now is good access to drugs from trials to give ourselves the best opportunity to play a vital part in our families’ life and fulfil meaningful roles in society for as long as possible.

At METUPUK we are painfully aware that metastatic breast cancer patients are
currently and literally dying for a cure.

Best of courage us all.