In Plain English

The main texts below are inspired by the xkcd 'Simplewriter', which allows only the use of the top thousand most common English words. We've deviated somewhat from that list (e.g. using the words cancer, medication, signal, tumor), but the spirit remains.

WHAT'S THE BIG PICTURE?

We study cancer, which happens when the tiny pieces that make up parts of the body start to grow out of control. This can happen in places all over the body, but for women this happens most often in the breast. Normal pieces of the breast sometimes get a “green light” signal to grow from the body, and there are lots of different such normal signals, like when a woman has a baby. Normal breast pieces will then stop growing when told to stop (like when the baby stops needing to nurse from the mother). Sometimes a breast piece will see a “green light” and never stop growing, and this will lead to the growth of a tumor.

"Cells", the microscopic basic structural units of all organisms.

One particular normal signal is stuck on in breast tumors about two-thirds of the time, but we have learned a lot about what this signal is and how it works. Doctors can tell whether this signal has gotten stuck on for each woman they help, and the woman can be given medication that will turn off the signal or stop tumors from seeing the green light. This stops the out-of-control growth in the breast, and woman that take these medications live longer and healthier than those women that don't.

This signal is through the 'estrogen receptor' (ER), which is the molecule that drives the cellular effects of the hormone 'estrogen'. Tumors that have ER are considered ER-positive, and women with ER-positive tumors can receive ER-blocking drugs ("anti-estrogens") like tamoxifen or aromatase inhibitors.

Medications that stop out-of-control breast tumor growth work very well and help a lot of women, but up to about half of the time, the treatment stops working and tumors start growing again. This is where we come in. We want to learn as much as we can about what breast tumors do when they see the “green light” signal, why they keep growing, and what they do to ignore medication. There is a lot to learn, because there are a lot of different kinds of pieces in the breast that may all pick a different way to grow when they have the green light. Also, every woman's breast tumor may each pick a different way to try to keep growing when a woman is taking cancer medication. Our plan is to make new types of medications that doctors can use to stop the breast tumors from seeing "green lights".

When tumors stop responding to ER-blocking drugs, they are called 'resistant' to treatment. The way tumors become resistant may be different for types of tumors, or may even be individual to each tumor.

WHAT IS 'ILC' AND WHY ARE YOU STUDYING IT?

One type of breast cancer that we focus our research on is a little different than other kinds of breast cancer. Most breast tumors will grow in to a ball (a solid lump in the breast), but the kind we study - invasive lobular carcinoma, or ILC - instead grows like a lot of long lines running in circles through the breast. For a long time, doctors guessed that ILC would act just like the other breast cancers, and they gave all women the same medications to try to turn off the “green light” signal. ​

You can see this 'single file' growth pattern below.

However, we are learning that this is not true, and that ILC tumors know how to just ignore some medications and never stop growing. Sometimes they may even use the medication as another green light! This tells us that the way that ILC see the green light, and what they do when they see it, must be very different than other breast cancers. We are working hard to learn what new types of medication might be needed to turn off the "green light" signal in ILC.

In the lab, ILC cells don't respond to ER-blocking drugs. They see drugs like tamoxifen as just another 'estrogen', and keep on growing.

These are diagnostic pictures of a slice of a patient tumor. The tumor slices are treated with colored dyes that help doctors identify tumor cells. Tumor cells are blue. Normal breast structure is pink.

This is a 'ductal carcinoma', the most common type of breast cancer. The whole picture is blue tumor cells, because this is a large, solid tumor.

This is an ILC tumor. The tumor cells (blue) snake and wind through the normal breast (pink). With no solid lump, ILC can be hard to detect by mammogram, and are difficult to surgically remove.

HOW DO YOU STUDY CANCER IN THE LAB?

One way we use to learn more is to use breast tumors that can grow outside of the woman on plastic plates as laboratory "models" of cancer. These tumors now grow forever (some have been growing for more than 40 years!). We can turn signals on and off, or give them the same medications that women receive, to see what the tumors do and how they act and grow.

These models are called "cell lines".​



It's just not possible to do some of these things to growing tumors in women, which is why we use tumor models growing on plates. Often, the way tumor models act can help us learn about breast cancer will act in women when they take medications. If we can learn all about how breast cancer models act when they see green lights and medications, then we will be able to make new medications for women with breast cancer.

In lab models, we can turn genes on and off, or even edit the genome. We can use drugs that are great 'tools' to understand biology, but that may not be ready for patients.


Tumor models are grown in plastic flasks, which keeps them in a 'clean' environment. Cells are fed with a nutrient-rich "broth" to keep them growing.

A special microscope can be used to look at the individual cells without removing them from the plastic flasks. We can see shape, size, and number of cells.

Can you guess which cell line is from an ILC tumor?

what is your overall goal?

​​We want doctors to have more choices of medications to give to women with breast cancer, especially when the medications that are used now stop working. This is very important for women with ILC tumors, since there are no medications just for these women, even though we are learning that the medications we have now might not work well enough for ILC.

Overall, we want to understand how medications that turn off “green lights” work in breast cancer, why they don't always work, and what we can do to make them work better.

That is, when breast cancer becomes resistant to anti-estrogen drugs.​