08-16-2020
THIS is why you donated tissue, or volunteered, or gave financial support, or requested samples, or supported us in-kind. This is why we are here. This is #ThePowerOfNormal.
Would you like to meet some of our fabulous researchers, and hear a bit about the work they are doing with KTB samples? Read on…
If you need definitions of terms you may find here, try opening our glossary.
Q: How did you find out about the Komen Tissue Bank, and why did it interest you?
When I decided to work on the association between pregnancy and breast cancer risk, I knew the major obstacle would be the collection of samples. Even if the UK, and Europe in general, have many excellent tissue banks, finding normal breast not affected by any disease is really hard. I therefore started to look online for more and more tissue banks, and that is how I found out about KTB. I was really impressed by the samples it provided, by all the necessary clinical information which came with those, and it really sparked my interest in all the potential findings these samples could lead to.
Q: What types of samples have you obtained from the Komen Tissue Bank?
We have received 60 tissue samples of frozen normal breast from pregnant and non-pregnant women at different age groups.
Q: What do you hope to discover/have you discovered in your research?
Several studies have observed a correlation between the age of a first-time full pregnancy and the risk of developing breast cancer. Women who have their first child at a younger age (below 24 years of age) have a lower risk of developing post-menopausal breast cancer compared to women who do not have a child. These women have even a lower risk compared to an older first-time mother (above 35 years of age). The molecular reason for this association, however, is still unknown.
The aim of our project is to look at how the mutation burden of the normal breast changes during age and during pregnancy, and to determine if there are any mutations in the cancer genes already present in the normal breast. This means we want to see how many mutations the normal cells accumulate during the years, and which effect this ultimately has in the development of breast cancer.
We have now completed the analysis of a first set of samples, and we can indeed detect several mutations in areas regulating cancer genes. We are really looking forward completing the analysis from all the samples and to determine how the changes in the mutation rates in the normal breast affect the cancerous breast.
Q: How will the Komen Tissue Bank samples help with your research? What value do they add?
The samples from KTB are at the core of our research, as we do all our analysis on those normal samples. The possibility of knowing exactly the age of pregnancy, the medication history, and the quality of the samples before actually receiving them, makes this set of normal breast unique. It would be very difficult for us to collect the same number of homogenous samples from a different source.
Q: Please explain in lay terms how your research might impact treatment options for BC patients in the future?
Delayed motherhood is often a feature in the wealthiest countries, as women have higher access to methods to control pregnancy, assisted reproduction and/or ultimately prefer to follow different life choices. While the choice of parenthood is personal, it is important for a woman to know that the probability of developing breast cancer after menopause can change with the age of first-time pregnancy. Once we know what factors are at the base of this association, we would be able to include women at risk, for example older mothers with a genetic predisposition, to a program of higher surveillance and screening after their pregnancy. Furthermore, knowing how changes in the DNA (mutations) occur in the normal healthy breast will form the basis of future scientific work on other diseases of the breast, even if they are not related to cancer.
Q: Our readers would love to know some personal information about you. Tell us anything at all that you feel comfortable talking about.
As a child, I never had straightforward career paths in mind. I defined myself as a potential archeologist, vet, astronaut and fashion designer… not in a specific order! You can see most of these professions have some sort of exploration in them, and that’s how I turned out to be a researcher, I guess. I’m so fascinated by what happens inside every single tiny cells of our body, which is like a little organized city on its own.
I now live in London, UK, but I come from Italy, and I also spent one year in Sweden. I therefore really enjoy what multiculturality brings to my daily life: different food to try, music to listen to, languages to learn, places to visit. I think I owe this to my parents. When I was little they bought a campervan and we visited lots of Europeans countries.
My favorite thing was, and I must say still is, going into local supermarkets and trying the typical food of the different places… my friends still laugh at me when I do this! Nowadays, however, I prefer a nice hotel to a campervan.
When I am not thinking science, I love baking. I am not really good at decorating cakes, but I still try and often laugh at my miserable efforts… but they still taste good. Very occasionally, they also look pretty, which is very satisfactory!
Q: How did you find out about the Komen Tissue Bank, and why did it interest you?
I was speaking at another university about my work, and I met with one of the original researchers who started the KTB. She encouraged me to use the KTB as a resource in my research.
Q: What types of samples have you obtained from the Komen Tissue Bank?
Frozen tissue sections from normal (not pregnant) and pregnant women.
Q: What do you hope to discover/have you discovered in your research?
Our bodies have a built-in cancer prevention strategy: the immune system. Cells of this complex system are constantly surveying the body looking for abnormal cells. Even the smallest of cancers, composed of just a few abnormally growing cells, will release danger signals that can be recognized by the surveilling immune system.
Once a tumor is recognized, activated immune cells destroy and clear the tumor cells. Although this process happens efficiently on a very regular basis, there are some cancer cells that will escape recognition by the immune system, subsequently developing into bona fide tumors.
Our research aims to understand how these cancer cells hide from the immune system: what mechanisms do they use to downregulate these danger signals? Understanding how cancer cells turn these signals off is the first step towards designing drugs that prevent cancer cells from escaping the watchful eye of the immune system.
In breast cancer, we propose that a hormone, progesterone, helps breast cancer cells hide from the immune system. Progesterone works by binding to a protein, the progesterone receptor, which in turn binds DNA and turns on genes involved in growth and survival.
Work from our lab has shown that the progesterone receptor can turn off some of the danger signals the immune system relies upon to recognize early tumors. This may also allow breast tumors to escape the surveilling immune system. We think this “immune-hiding” ability of progesterone is a normal, critical function of progesterone during pregnancy, to keep the immune system at bay and prevent rejection of the developing fetus.
Our hypothesis is that this normal function of progesterone is used by tumor cells as a way of hiding from the immune system.
Q: How will the Komen Tissue Bank samples help with your research? What value do they add?
To determine what goes “wrong” in breast cancer, we have to understand what goes “right” in normal cells – we need to understand the normal functions and properties of proteins in their normal state. We used tissue samples from donors to compare levels of these “warning signals” in pregnant vs non-pregnant samples. We found that these signals are indeed decreased in pregnant samples, indicating that this may be a normal role for these danger signals.
Q: Please explain in lay terms how your research might impact treatment options for BC patients in the future?
We propose that blocking the progesterone receptor, thereby alerting the immune system to the presence of these early, small breast tumors, could be a novel mechanism for preventing and treating breast cancer.
Q: Our readers would love to know some personal information about you. Tell us anything at all that you feel comfortable talking about.
I have a wonderful, supportive, and crazy busy (!!) family. My husband and I both met in graduate school at the University of Chicago while pursuing our PhDs – mine in Cancer Biology, his in Astrophysics. It turns out that while we are both scientists, trying to talk about clusters of galaxies vs DNA from cancer cells is harder than you think! We have two young kids, Jacob (7) and Ben (4), that keep us very busy.
In academia, people move around a lot: we have lived in Colorado, Chicago, Baltimore, St. Paul/Minneapolis, and now Kansas City. While in Chicago and Minneapolis, my husband and I got into curling! Such a fun sport, especially for nerdy science types. I have always wanted to be a scientist, but initially thought my direction was supposed to be medicine. After a failed shadowing attempt in the emergency room that ended up with me as the patient, I realized that research science was really the best way for me to impact patients’ lives. I’ve never looked back since!
Q: How did you find out about the Komen Tissue Bank, and why did it interest you?
We believe that the key to unlocking the mysteries of breast cancer lies in our understanding of normal breast development and homeostasis. One of the research themes in my lab is looking at the physiology of lactation and how the breast epithelium changes in response to lactation. To do this, we mainly make use of mouse models. But ultimately, we want to make sure that what we see in rodent models also occurs in human tissue. By having access to lactating breast tissue through the KTB, we have been able to do just this and validate our findings in human samples. This is a really important step in our science.
Q: What types of samples have you obtained from the Komen Tissue Bank?
Tissue biopsies from women who have never given birth, those who are currently lactating, and from women who have children but who have stopped breastfeeding.
Q: How will the Komen Tissue Bank samples help with your research? What value do they add?
The KTB is one of the only sources of normal (non-cancer) breast tissue samples in the world that includes samples from actively breastfeeding women. In my lab, we investigate changes in the mammary epithelium in rodent models and have been using the KTB samples to determine whether the same changes occur in human tissue.
Q: Please explain in lay terms how your research might impact treatment options for BC patients in the future?
Our research seeks to understand the cellular hierarchy in the breast and the pathways that regulate adult breast stem cells. We also study the unique and extraordinary capacity of the breast to sustain multiple cycles of pregnancy and lactation, which a remarkable feat of tissue regeneration. We hope that a greater understanding of the processes governing growth, death and remodeling under physiological (normal) conditions will help to identify new strategies for curbing the uncontrolled growth, death resistance and remodeling that are common to all breast cancers.
Q: Our readers would love to know some personal information about you. Tell us anything at all that you feel comfortable talking about.
I am relatively early on in my career (I only got my PhD in 2012), however, during this short period of time I have had the opportunity to do some amazing science in the field of breast physiology and cancer in the US (NIEHS, North Carolina), the UK (University of Cambridge) and Australia (Mater Research Institute). When I moved to the US I adopted a stray cat. I named her Bronte, as I was reading books by the Bronte sisters at the time. Bronte has moved around the world with me. First to Cambridge (via London) and then to Brisbane (via Melbourne). She is very well traveled!
