Research on chemo in breast cancer

Lily55

http://www.telegraph.co.uk/science/2017/07/05/chemotherapy-may-spread-cancer-trigger-aggressive-tumours-warn/?WT.mc_id=tmg_share_fb

Lily55

http://stm.sciencemag.org/content/9/397/eaan0026

Tinkerbells

This is a surprising result. I would be interested to see the methodology of the study. I suspect it is cellular based, in the lab, and not translated to a human population.

Still, it's pretty shocking

besa

https://medicalxpress.com/news/2017-07-neoadjuvant...

Another abstract of the same study.

MTwoman

The summary of the actual study:

"Breast cancer cells disseminate through TIE2/MENA^Calc/MENA^INV-dependent cancer cell intravasation sites, called tumor microenvironment of metastasis (TMEM), which are clinically validated as prognostic markers of metastasis in breast cancer patients. Using fixed tissue and intravital imaging of a PyMT murine model and patient-derived xenografts, we show that chemotherapy increases the density and activity of TMEM sites and Mena expression and promotes distant metastasis. Moreover, in the residual breast cancers of patients treated with neoadjuvant paclitaxel after doxorubicin plus cyclophosphamide, TMEM score and its mechanistically connected MENA^INV isoform expression pattern were both increased, suggesting that chemotherapy, despite decreasing tumor size, increases the risk of metastatic dissemination. Chemotherapy-induced TMEM activity and cancer cell dissemination were reversed by either administration of the TIE2 inhibitor rebastinib or knockdown of the MENA gene. Our results indicate that TMEM score increases and MENA isoform expression pattern changes with chemotherapy and can be used in predicting prometastatic changes in response to chemotherapy. Furthermore, inhibitors of TMEM function may improve clinical benefits of chemotherapy in the neoadjuvant setting or in metastatic disease."

So yes, this was a murine model, NOT a patient based study. Also, they looked at what prevents this from happening, "TMEM activity . . .were reversed by . . " (above).

The Telegraph article conveniently leaves those facts out. It is inflammatory.

BarredOwl

This is primarily a preclinical mechanistic and biomarker study, with some implications for potential biomarkers and potential therapeutics.

Karagiannis (2017): http://stm.sciencemag.org/content/9/397/eaan0026

We know from clinical trials that patients do receive clinical benefit from neoadjuvant chemotherapy. However, such treatment is not 100% effective and some patients go on to suffer distant metastatic recurrence. The observations in this study suggest one potential mechanism that may explain some of the observed treatment failures. Understanding a potential mechanism for treatment failure in some cases does NOT negate the existing clinical evidence demonstrating improved outcomes from treatment. Indeed, another popular press feature noted that lead author Dr George Karagiannis says the findings, published on Wednesday, should not deter patients from seeking treatment.

The results have implications for the potential future use of "TMEM score increases and MENA isoform expression pattern changes" as biomarkers for monitoring neoadjuvant treatment, perhaps permitting adaptation of treatment plan in select patients. However, additional research and clinical validation trials are required before implementation in clinical practice.

As the abstract notes, perhaps researchers will be able to further improve outcomes of treatment in the future if they can thwart this process either via administration of a TIE2 inhibitor (e.g., rebastinib) or by inhibiting MENA activity:

>> "Furthermore, inhibitors of TMEM function may improve clinical benefits of chemotherapy in the neoadjuvant setting or in metastatic disease."

BarredOwl