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New hope for stopping the spread of metastatic breast cancer

A new era of targeted treatments for metastatic cancer may be around the corner, an expert says, as new research shows some primary breast tumours stop their own spread by harnessing the body’s innate immune system.

Research published in Nature Cell Biology this week found that in both mice and humans, primary breast tumours elicited an inflammatory response through 1L-1β to freeze the growth of breakaway cancer cells in other parts of the body.

Among 215 patients with lymph node positive breast cancer, those with high 1L-1β expression in the primary tumour had improved overall survival relative to those with low 1L-1β expression, retrospective analysis showed.

The authors showed through a series of mouse models that the primary tumour was driving 1L-1β expression to lock secondary cells into a state where they could not proliferate.

For instance, mice with a primary tumour were less likely to develop macrometastases when injected with metastasis-inducing cancer cells from that same tumour, compared with mice lacking the primary tumour. Furthermore, when the 1L-1β inflammatory response was blocked – either at the primary tumour or metastatic sites – metastatic colonisation occurred.

 A new era

Study co-senior author, Dr Christine Chaffer from the Garvan Institute of Medical Research said the findings constituted “a great advance, and one that suggests a novel way to combat metastases.”

“We think this immune system activation by the primary tumour is an unintentional by-product of the metastatic process, and one that we can hopefully enhance to fight cancer.”

“There has been so little progress until now in understanding the biological processes driving metastases,” she said. “This new discovery – combined with new single-cell sequencing technology which is able to tease out the composition of individual tumours and potentially identify aggressive tumour cell sub-populations – will hopefully yield a new era of targeted therapies for metastatic patients in the next 5-10 years.”

Dr Chaffer said she was optimistic the findings would bring hope to future patients with triple negative breast cancer – a disease which accounts for 25% of breast cancer cases but has an exceptionally poor prognosis. Some 60% of patients experience recurrence that is metastatic and/or chemo-resistant.

 ‘Innate’ not ‘adaptive’ immunity

Melanoma research has had the lion’s share of cancer breakthroughs in the last decade, especially with the advent of immunotherapy. However Dr Chaffer noted that such immunotherapy had not been shown to work well in breast cancer.

“It’s now apparent that the adaptive immune response plays a major role in melanoma, whereas this is not necessarily the case in breast cancer. Our research shows the important role of the innate immune system in suppressing breast cancer,” she said.

Breast screening in Australia: more harm than good?

 

Findings from two new NSW studies point to substantial overdiagnosis of early breast cancer and suggest screening may in some cases be causing more harm than benefit.

The studies, authored by researchers from the Universities of Sydney and New South Wales, looked at data from all women in New South Wales who received a breast cancer diagnosis from 1972 to 2012, spanning both the pre-screening and screening years.

One study, which tracked diagnoses of ductal carcinoma in situ (DCIS), saw a 100-fold increase from 0.5 to 16.8 cases per 100,000 women over the period. It found that DCIS incidence has continued to rise despite screening being now well established for over two decades.

The second study, looking at cancer stage at diagnosis, found that the incidence of all stages of breast cancer has increased over the past 40 years, with the greatest rise occurring during the screening era in women aged 50-69 years.

The researchers say that since the purpose of screening is to detect early disease in order to prevent later metastases, it would be logical to see some reduction in advanced disease as screening numbers stabilised.

But that’s not what the figures show. While many more women are being diagnosed and treated for DCIS and early disease, this is not preventing later stage disease and associated metastases.

“Our findings suggest that some of the expected benefits of screening may not have been realised and are consistent with overdiagnosis,” the authors write.

“That distant metastases do not appear to be affected by mammography is a concern given prevention of advanced disease is a key aim of screening, along with breast cancer mortality.”

What may be happening, the authors suggest, is that most of these early breast cancers now being picked up through screening would never have developed into fatal disease had they gone undiagnosed, or would have developed so slowly that older women would have been more likely to die of something else first.

And the result is that while many more women are being diagnosed and treated for DCIS and early disease, this is not preventing later stage disease.

Incidence rates of DCIS continued to rise even after the number of women being screened stabilised, the researchers found. This may be due to a switch from film to the more sensitive digital mammography, as well as other technological advances in diagnosis, including breast ultrasound, MRO and tomosynthesis.

Currently all women diagnosed with DCIS receive treatment, and there is also a trend towards more aggressive treatment such as contralateral mastectomies. The authors warn that the risk of overtreatment is “substantial, with serious effects on quality of life”.

“Our findings suggest that we should rethink strategies for the detection and management of DCIS,” they write. Their findings “lend support to trials evaluating de-escalation of therapy for certain types of early-stage breast cancer, such as DCIS”.

While it’s true that breast cancer mortality rates have dropped considerably over the period studied, the authors say this may be primarily due to improved treatment options rather than screening.

Screening in NSW has been free for women since 1988, and since 1991 women aged 50-69 have been targeted with letters of invitation.

You can access the two studies here and here.