Ariana Stephen / Sun Contributor

October 19, 2020

How Cornell Adopts a Multidisciplinary Approach In Tackling Breast Cancer

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Each October, Americans honor their loved ones battling breast cancer with charity fundraisers, pink clothing items and ribbons. Breast Cancer Awareness Month often comes as a somber reminder of lives lost to the devastating disease and all that researchers have yet to understand. But what exactly is breast cancer, and how can it currently be treated?

Prof. Claudia Fischbach, biomedical engineering, and Dr. Eleni Andreopoulou, breast oncologist at Weill Cornell Medical Center, dove into the biology of breast cancer from their perspectives on the front lines of cancer research and treatment.

According to Fischbach, breast cancer arises from abnormal cells that develop from errors in the genetic code. These mutations can cause the cells to grow uncontrollably in the breast tissue, resulting in a clump of cells called a tumor.

However, what makes breast cancer so dangerous is its malignant heterogeneity — certain cancers are hardwired to invade, migrate and spread, according to Andreopoulou.

“It follows a pattern of dynamic evolution — the disease is not static,” Andreopoulou said. “It’s the nature, and the biology of each tumor. Each cancer diagnosis is unique for each individual.”

Everything from the tumor’s genetic makeup to a patient’s hormone balance and lifestyle choices can affect the clinical course of the disease, as well as how well patients might respond to certain treatments, Andreopoulou said.

The treatment of breast cancer is often guided by the types of receptors on a patient’s tumor cells, according to Andreopoulou. One subtype — hormone-receptor positive breast cancer — means that tumor cells have receptors for hormones required for their growth, like estrogen or progesterone.

According to Andreopoulou, tumors with hormone receptors can be more effectively treated, because drugs that cut off hormone supply to these tumor cells — used in tandem with drugs targeting cell growth and division — can halt the progression of the cancer.

Other breast cancer subtypes that lack both hormone receptors and a specific growth-promoting protein, HER2, respond to fewer drugs, and require a more aggressive treatment approach that’s mainly limited to chemotherapy, which is toxic to cells, Andrepoulou said.

Beyond the biology of cancer cells, tumor growth is influenced by how those cells interact with their surrounding environment. According to Fischbach, there are studies that support this conclusion because they demonstrate how  tumor cells implanted into healthy, actively growing embryos can never develop into cancer.

“If you put them into an environment that is permissive, it’s like a seed in soil,” Fischbach said. “If the soil is right, the seed grows, and vice versa. If the soil isn’t right the seed doesn’t grow. It’s the same with cancer.”

According to Fischbach, since cancer cells require specific environments to grow, they aren’t likely to survive the compromising conditions involved in spreading to different parts of the body. But if they do find a new site to grow, this condition — called metastasis — can be incredibly dangerous.

For example, Fischbach said t breast cancer cells prefer to grow in environments with stiff, dense tissue. These cells are prone to migrating to niches in the bone, where they can easily grow and proliferate.

According to Fischbach, the importance of tissue density can be seen even prior to diagnosis, when women often feel a hard, palpable lump of tissue in their breast that is characteristic of cancer. This lump is made stiff by the development of thick scar tissue around the tumor cells, which fosters an environment that can trigger a tumor to become aggressive.

“Scar tissue is…very densely packed, and one can mimic those properties using biomaterials. You can basically make biomaterials that are softer, or stiffer…and then look at how that affects tumor cell behavior,” Fischbach said. “That gives you additional insights into why cancers develop.”

In her research lab, Fischbach uses such biomaterials to engineer artificial environments that mimic the human body, allowing for a more accurate portrayal of tumor growth that transcends the limitations of traditional cancer research.

“In a Petri dish on a plastic surface, there are no other cell types, no blood vessels … no factors in space and time that might be affecting things,” Fischbach said. “As engineers we have the capability to mimic some tissue structures that better recapitulate how these cells behave in our body.”

COVID-19 also pushed the boundaries of multidisciplinary healthcare delivery at Weill Cornell, with essential care heavily relying on technological innovations in order for providers to safely interact with their patients.

Weill Cornell physicians collaborated with the Englander Institute for Precision Medicine to employ HoloLens — a 3D mixed reality device that broadcasts holograms over physical space. While her physician’s assistant wore the HoloLens headset during a patient visit, Andreopoulou could broadcast live clinical records from her computer at home while voicing her insights through videoconference, allowing her “to continue providing care as close as [possible to her] being physically there.”

“For us, piloting this project has been significant progress forward in how we can maintain safe [breast cancer] patient care without interrupting the integrity and the importance of multidisciplinary care,” Andreopoulou said. “That’s what technology is all about.”

Another potential way to battle cancer is sequencing the DNA of the tumor itself. Fischbach explained that by sequencing the genomes of tumors and finding out the variability of cells in the tumor in a large number of patients, medical professionals can compare this information to how those patients responded to different treatments. This could help doctors to figure out specific genetic sequences in tumors that are predictive of treatment response.

However, Cornell collaboration at the intersection of genetics, engineering and technology has pushed the boundaries of precision medicine and allowed for the development of a revolutionary way to study patient’s tumors — organoids.

Organoids are tissue cultures that replicate the complexity of a patient’s own cells while outside the body. If grown using a patient’s tumor cells, the organoid can be used to support rapid drug testing, which can ultimately fast-track the development of effective therapies and broaden the spectrum of patients that can be treated, according to Andreopoulou.

Because of its wide array of applications, organoids can be used to further understand why some patients respond poorly to chemotherapy, develop novel strategies to identify these patients in the clinic and create alternate treatments to improve patient outcomes.

“We integrate technology into patient care very early on with all the amazing possibilities we have now — tumor sequencing, learning more and expanding our knowledge,” Andreopoulou said. “We’re trying to exploit all these opportunities by tailoring treatment to the molecular vulnerabilities that patients have.”

Breast cancer affects millions of women and families across the globe, but interdisciplinary scientific research is paving the way for better testing and treatments.  With new tools such as tumor sequencing, affected people can live long, healthy and happy lives.

“Being trained as an interdisciplinary scientist is going to be important — not just for cancer research, but for everything,” Fischbach said. “You need to be able to bring in all of these different aspects in order to move forward.”