Nav: Home

Breast cancer: An improved animal model opens up new treatments

March 03, 2016

EPFL scientists have developed an animal model for breast cancer that faithfully captures the disease. Tested on human breast tissue, this the most clinically realistic model of breast cancer to date.

Breast cancer is the most common cause of cancer-related deaths worldwide, affecting one in eight women. There are different types of breast cancer, but one type in particular accounts for almost three quarters of all breast tumors. These tumors feature a receptor for estrogen, and very often become resistant to hormone therapy. Despite their high frequency, these "estrogen receptor-positive" tumors have been difficult to research because the animals we test drugs on are often not relevant to the clinic. Publishing in Cancer Cell, EPFL scientists have now developed the most biologically faithful animal model for estrogen receptor-positive breast cancer. Their model has also been tested on human breast tissue in a pre-clinical context.

About 90 percent of tested new cancer drugs fail. The reason, in part, is that the animals on which these drugs are tested often fail to capture the complex biology of the cancers they are meant to represent. This biological inaccuracy frequently gives rise to data that seem encouraging at first but are then not matched in humans. The drug fails and pushes research back to square one.

Some of the best pre-clinical animal models for breast cancer are made by injecting human breast tumors into the fatty tissue of the animal's breast or its flank - the animal itself is usually a mouse. Nevertheless, these animal models - called "patient-derived xenografts" - under-represent the most frequent and lethal breast tumors, the estrogen receptor-positive type. The reason is that after injection into the animal, the tumor cells frequently die off and fail to proliferate.

The lab of Cathrin Brisken at EPFL has now developed the first xenograft to better represent the biology of estrogen receptor-positive breast tumors in humans. Postdoc George Sflomos and colleagues show that the mouse's milk ducts are the key for the physiological growth of estrogen receptor-positive breast tumors, as they offer the injected cells a more suitable environment to grow and proliferate in rather than the conventional routes (the mammary fat pad and the flank). By injecting cells from an estrogen receptor-positive tumor into the mouse's milk ducts, the researchers could improve the survival rate of the tumor cells for the first time ever.

To test their new xenograft idea, the team obtained breast cancer cell lines and tumor tissues from estrogen receptor-positive breast cancer patients, and injected them directly into the milk ducts of mice. The results were remarkable: All the new xenograft models that were tested faithfully mimicked actual patient tumors in terms of histopathology and even molecular biology.

"With this breakthrough, breast cancer disease, progression and metastasis, now become amenable to study," says Sflomos. "We can now study crucial factors, such as the action of hormones and molecular responses to therapies, for the first time in a relevant context. But more importantly, this model opens up new opportunities not only for the development but also for the evaluation of breast cancer therapies."
-end-
This work included a collaboration of EPFL's Swiss Institute for Experimental Cancer Research (ISREC), the Lausanne University Hospital (CHUV) and the University of Tartu (Estonia). It was funded by the European Union Seventh Framework Programme (Innovative Medicines Initiative Joint Undertaking/PREDECT consortium), the European Federation of Pharmaceutical Industries and Associations, Oncosuisse and the Swiss National Science Foundation.

Reference



Sflomos G, Dormoy V, Metsalu T, Jeitziner R, Battista L, Scabia V, Raffoul W, Delaloye J-F, Treboux A, Fiche M, Vilo J, Ayyanan A, Brisken C. A preclinical model for ERα-positive breast cancer points to the epithelial microenvironment as determinant of luminal phenotype and hormone response. Cancer Cell 14 March 2016. DOI: 10.1016/j.ccell.2016.02.002

Ecole Polytechnique Fédérale de Lausanne

Related Breast Cancer Articles:

Does MRI plus mammography improve detection of new breast cancer after breast conservation therapy?
A new article published by JAMA Oncology compares outcomes for combined mammography and MRI or ultrasonography screenings for new breast cancers in women who have previously undergone breast conservation surgery and radiotherapy for breast cancer initially diagnosed at 50 or younger.
Blood test offers improved breast cancer detection tool to reduce use of breast biopsy
A Clinical Breast Cancer study demonstrates Videssa Breast can inform better next steps after abnormal mammogram results and potentially reduce biopsies up to 67 percent.
Surgery to remove unaffected breast in early breast cancer increases
The proportion of women in the United States undergoing surgery for early-stage breast cancer who have preventive mastectomy to remove the unaffected breast increased significantly in recent years, particularly among younger women, and varied substantially across states.
Breast cancer patients with dense breast tissue more likely to develop contralateral disease
Breast cancer patients with dense breast tissue have almost a two-fold increased risk of developing disease in the contralateral breast, according to new research from The University of Texas MD Anderson Cancer.
Some early breast cancer patients benefit more from breast conservation than from mastectomy
Breast conserving therapy (BCT) is better than mastectomy for patients with some types of early breast cancer, according to results from the largest study to date, presented at ECC2017.
One-third of breast cancer patients not getting appropriate breast imaging follow-up exam
An annual mammogram is recommended after treatment for breast cancer, but nearly one-third of women diagnosed with breast cancer aren't receiving this follow-up exam, according to new findings presented at the 2016 Annual Clinical Congress of the American College of Surgeons.
Low breast density worsens prognosis in breast cancer
Even though dense breast tissue is a risk factor for breast cancer, very low mammographic breast density is associated with a worse prognosis in breast cancer patients.
Is breast conserving therapy or mastectomy better for early breast cancer?
Young women with early breast cancer face a difficult choice about whether to opt for a mastectomy or breast conserving therapy (BCT).
Breast density and outcomes of supplemental breast cancer screening
In a study appearing in the April 26 issue of JAMA, Elizabeth A.
Full dose radiotherapy to whole breast may not be needed in early breast cancer
Five years after breast-conserving surgery, radiotherapy focused around the tumor bed is as good at preventing recurrence as irradiating the whole breast, with fewer side effects, researchers from the UK have found in the large IMPORT LOW trial.

Related Breast Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...