Scientists identify a potential new treatment option for lobular breast cancer

A drug currently being tested in clinical trials for a rare blood cancer could also be used to treat lobular breast cancer, according to a study published in the journal Cancer Research.

Scientists at The Institute of Cancer Research, London, found that the drug – a LOX inhibitor – can slow the growth and spread of lobular breast cancer in mice.

The researchers, based at the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR), now hope to progress the drug to clinical trials for this under-researched type of breast cancer.

Identifying a gap in research

Invasive lobular breast cancers make up 15 out of every 100 breast cancers. Because these tumours infiltrate the surrounding tissue in single cell lines – rather than a tumour mass – they are difficult to detect through clinical imaging and it is hard to determine how big they are. This means that they are excluded from most clinical trials, as the impact of the treatment on tumour size needs to be measured.

Currently, there are no approved drugs that specifically target this disease, and it is treated in much the same way as other types of breast cancer, despite the fact that lobular tumours grow differently from other breast cancers, tend to spread differently, and have some distinct molecular features.

A key to fit the LOX

Lobular breast cancer is difficult to study in the lab, so the team used samples donated by people with lobular breast cancer to grow lobular tumours in the milk ducts of mice. In doing so, they were able to accurately mimic the diversity of lobular tumours seen in people.

Some lobular breast cancer cells also release an enzyme called LOX, which allows the cells to modify surrounding collagen fibres and to increase tissue stiffness. When this happens, it improves the ability of the cancer cells to grow and spread.

The research team treated the tumours with a drug called a LOX inhibitor, which is already in early clinical trials for the treatment of a rare blood cancer called myelofibrosis. Collagen fibres play an important role in this disease of the bone marrow, and the team found that lobular breast cancer cells also rely on these fibres. The single cell files of lobular cells grow and spread along collagen fibres.

The drug was able to disrupt these interactions between lobular breast cancer cells and supportive collagen fibres in their surrounding environment. Disrupting these interactions decreased tumour growth and spread, and the mice involved in the study tolerated the drug well with minimal side effects.

Increasing treatment effectiveness

The team is searching for increased activity in certain genes that is closely linked to how well the tumour responded to the drug. In the future, this could be used to help doctors predict how people diagnosed with lobular breast cancer may respond to LOX inhibitor treatment.

Based on their findings, the researchers think that high activity of the gene called JUN may help lobular breast cancers resist the standard hormone therapy, tamoxifen. The team believe that in the future, combining LOX inhibitors with standard hormone therapy currently used to treat lobular breast cancers could enhance the effectiveness of hormone therapy.

Almost 20 years ago, researchers at the ICR discovered that the LOX enzyme is crucial in promoting cancer spread. Then, in 2017, another ICR team designed and validated a drug to target LOX, which they showed slowed breast cancer tumour growth and metastases in mice.

Accelerating progress

By creating models of lobular breast cancer in mice that more closely mimic the disease in people, this research has improved the tools available to study lobular breast cancer, helping scientists around the world to better understand the disease.

The team are hopeful that, since the drug is already in clinical trials for another cancer, it will soon provide a new treatment option for people living with lobular breast cancer.

Professor Cathrin Brisken, Leader of the Endocrine Control Mechanisms Group at The Institute of Cancer Research, London, said:

“Lobular breast cancer has historically been neglected. It’s a cancer that’s difficult to see on scans, and it’s difficult to model. My team have created a new model, by putting the tumour cells inside the milk ducts of mice. This allows the cells to find the environment they are used to, and to grow, so that we can study them.

“Now, these exciting developments are happening. I don’t want to give false hope, but things are moving in the right direction, and we have come a long way.

“The next stage for this research will be clinical trials – we are currently applying for funding to launch a trial with 91 patients.”

Dr Renee Flaherty, Postdoctoral Training Fellow at The Institute of Cancer Research, London, said:

“Working on lobular breast cancer in the lab can be really challenging, as the models take a long time to grow. It requires a lot of dedication and patience, and many researchers have contributed along the way. Ultimately, we’ve uncovered some interesting aspects of its biology that we hope will open up new possibilities for therapeutic targeting in the future.

“Being part of the lobular breast cancer research community has been especially motivating. It’s exciting to see the progress being made, and I’ve been particularly inspired by the patients and advocates I’ve met, whose experiences and commitment to research have driven me throughout this work.”

Image: Invasive Lobular Carcinoma cells (yellow) growing in single files along collagen fibres (red). Credit: Dr Renee Flaherty, The Institute of Cancer Research, London.