Next Gen in 10: Hormone Therapy and Cancer Risk in Real-World Data

In this episode, we’re joined by Tessa Woodside, MSc student at UBC, whose research examines hormone therapy use and breast and endometrial cancer risk using large, real-world health data from BC and Alberta.

Tessa walks us through her research questions, methods, early findings, and why the details of hormone therapy matter when we talk about cancer risk.

🎧 Tune in to hear how population-level data can answer questions clinical trials often can’t.

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Transcript

00:00:02 Intro 

Thanks for listening to the GOSH Podcast, the Gynecologic Oncology Sharing Hub. We share real, evidence-based discussions on gynecologic cancers featuring stories from patients, survivors, researchers, and clinicians. Our podcast is produced and recorded on traditional unceded territories of the Musqueam, Squamish, and Tsleil-Waututh Nations. It is produced by the Gynecologic Cancer Initiative, a BC-wide effort to advance research and care for gynecologic cancers. 

00:00:36 Sabrina 

All right, welcome everyone. My name is Sabrina and I'd like to welcome you back to our new segment on the GOSH podcast, which is called Next Gen Intent, where we featured trainee researchers. Today we are joined by Tessa Woodside, who is a master's student at the University of British Columbia in the Women and Children's Health Sciences Program. Supervised by Dr. Aline Talhouk, her thesis examines women's health with a focus on breast and endometrial cancer in relation to hormone therapies. Her research is supported by a CIHR Canadian Graduate Research Scholarship. Welcome to the podcast, Tessa. 

00:01:14 Tessa 

Thank you for having me. I'm excited. 

00:01:16 Sabrina 

Thank you for joining us. I was thinking we could start by just giving us a bit of a background on your research topic, as well as the gap that you are aiming to fill with your research. 

00:01:28 Tessa 

Yeah, definitely. So my lab is the Uterine Health Research Lab, and we primarily focus on health during and after the menopausal transition. And my research fits really closely with our lab's kind of broader focus on reproductive aging and cancer risk, as I'm studying hormone therapy use and its relation to breast and endometrial cancer. So I guess I'll give a bit of a background on endometrial cancer. Too much estrogen without enough progesterone can overstimulate the cells in the endometrium and this leads to a condition called endometrial hyperplasia where the endometrial cells grow uncontrollably and this can increase your risk for endometrial cancer. So this can happen for many things like taking estrogen-only replacement therapy or naturally through obesity in a high BMI where there is already naturally occurring estrogen. And progestogen is often given to balance out that high estrogen. However, there is some concern that progestogen therapies increase the risk of breast cancer. Now, this kind of originated from a study back in 2002, the Women's Health Initiative. They conducted a randomized controlled trial on menopausal hormone therapies, and they reported a strong link between the estrogen and progestogen hormone therapy group and breast cancer. So this caused a lot of concern at the time, and many women were wrongly encouraged to stop taking hormone replacement therapy. But now we're seeing a lot more recent studies that are kind of disproving this original study and suggesting that the risk of progestogen hormone therapy may be modest or even non-existent. So my study hopes to provide some more clarity by looking at how different types of hormone therapy, so this includes contraceptives and menopause hormone therapy, and how they affect cancer risk. And this will be done using real world population data from both BC and Alberta, but for this podcast, I'm just going to be focusing on the BC population. 

00:03:24 Sabrina 

Very interesting. Interesting. Great, great background on why, you know, this topic is very timely and interesting. So how do you plan on addressing this question? Because of course, you could come to this with many different angles. So what are your research questions or your objectives? 

00:03:43 Tessa 

So I think the main goal of my study is to understand how progestogen use among females in BC is related to cancer risk. And I'm particularly interested in breast and endometrial cancer. So I have two more specific aims. Firstly, I want to examine how different hormone therapy factors, so the type of hormone therapy, how it's administered, the timing of administration, and the duration, how this all affects endometrial and cancer rates. Second, I also want to look at cancer rates while accounting for individual-level risk factors, such as BMI, smoking status, and alcohol use. So for this, I'm going to be using a validated epidemiological risk modeling tool called the Pfeiffer model, and this will calculate someone's baseline cancer risk so that we can see how hormone therapy use will interact with each person's unique risk profile. 

00:04:37 Sabrina 

Very interesting. Okay, so how are you going to go about answering those questions or sort of what's your methodology? 

00:04:44 Tessa 

Yeah, so my study is a retrospective study. Essentially, I'm going to be looking at exposures and outcomes that have already occurred between 2000 and 2023. So I'll be using administrative health data from BC. Admin data includes kind of all records out there, so pharmacy records, cancer registry databases, vital statistics, and hospital records. And this will cover pretty much everyone living in BC who is registered with MSP. This gives a very large and representative sample. And so to access these data sets, I'm using population data BC. Now, this kind of links all these data sets together using unique study IDs. And it will allow me to get a more complete picture of my cohort, as I can see all pharmacy records, cancer outcomes, and health procedures per person. And within this cohort, I'm going to be classifying hormone therapy exposure by four main groups. So first, the type of hormone, the method of administration, the duration, and then the age at initiation. And I'm looking at mainly just endometrial and breast cancer outcomes as my primary outcome. In my second aim, I'm going to be integrating data from CANPATH. This is the Canadian Partnership for Tomorrow's Health. It's a large national cohort study that collects various data on health and lifestyle factors, and it includes over 1 million Canadians in the study, so it's quite big. This will give me any additional information on individual factors that I'll be needing for my second aim. And so this will kind of provide another level to, or that the admin data will be missing because I'll have access to their BMI if they've smoked, if they drank, et cetera. And then using the Pfeiffer model, I will then generate those personalized cancer risk scores to see how hormone therapy modifies that risk. 

00:06:41 Sabrina 

Very interesting. That sounds like a lot of work. So can you tell us, you know, where you are so far in your research and if you've had any interesting findings thus far? 

00:06:51 Tessa 

Yeah, so I unfortunately can't talk about any of my results right now because I don't have approval from ethics, but I can discuss some of my hypothesis for you guys. So I think the main thing that I'm expecting to see is lower endometrial cancer rates in the progestogen-containing hormone formulations. This is very standard in the literature since we know that progesterone and progestogens are risk reducing for endometrial cancer. For breast cancer, I expect a slightly higher incidence in the progestogen-containing hormone therapies, but I think this increase will be very slight and likely insignificant just based off of the recent literature that's out there. And finally, I hypothesize that individual-level risk factors like BMI will further modulate those cancer incidences. 

00:07:41 Sabrina 

Okay, well, I guess we'll be excited to see the results of your study when they come out eventually. So I would want to talk about hormone therapy in general because it can mean a lot of different things and there's a lot of different hormones, different doses, different ways of taking them. So based on your research, why do you think these differences matter when we're talking about cancer risk? 

00:08:04 Tessa 

Yeah, I think it's really important to know that not all hormone therapies are the same and treating them as they are the same can be misleading. So different classes like estrogens, progestogens, and combination therapies, they all act differently in the body and are all prescribed for different things. And how a hormone is delivered also matters. For example, oral therapies, they have a more systemic effect since they're absorbed through the bloodstream. While when you have an intrauterine device or a vaginal tablet or a vaginal cream, that will add to more locally. And so even within gen and the duration that you're exposed to the hormone will also influence risk and understanding those nuances, I think is key because hormone therapies can be protective against some cancers and potentially risky for others. So one of the main examples is ovarian cancer. And I know you guys talked about this on your previous Next Gen in 10 podcast, but It's combined oral contraceptives are protective against ovarian cancers. And we also know that for endometrial cancer, estrogen therapies are a risk factor for endometrial cancer, while progestogens are protective against it. So I think it's all about balance and proper education and how can we translate our findings to the general public so that we don't cause any misinterpretations or fears. 

00:09:30 Sabrina 

Yeah, I think those are all great points. And thank you for taking the time to highlight the nuance in the different types of hormone therapy. So another question we have is because you're using large real world data from both BC and Alberta, what kinds of questions do you think that this specific type of data can help answer that smaller studies or even clinical trials often can't? 

00:09:53 Tessa 

Yeah, so when you're working with large data, you have access to so many people. And I think one of the biggest advantage is the scale. So I have over a million people in my cohort that I'm looking at, and I'm able to capture relatively rare outcomes like breast and endometrial cancer diagnosis and still get reliable and generalizable results. So it also allows us to look at real world hormone therapy use. When you have a randomized control trial, you're kind of given hormone therapies under idealized conditions. And when you have access to the pharmacy records, you're able to see what actual Canadians or what actual people living in BC are taking. So for example, we can examine whether cancer risk differs based off of how long someone is using hormone therapies for, or if the age at which they start has a difference on cancer risk as well. And these questions are often really hard to ask in smaller randomized controlled trials because it just takes so much time to even develop cancer. But I think it's also important to remember that retrospective cohort studies, they can't prove causation the way that randomized controlled trials do. But they can often provide a lot of really important data for looking at associations between two of the things. 

00:11:11 Sabrina 

Yeah, absolutely. again, I'm excited to see what your study shows. I think it's a very interesting topic, very timely. I know many people will probably follow up on this podcast episode to see what your results are. To conclude today's episode, I wanted to ask you what we'd like to ask all of our trainees, which is if you could only say one thing to everyone who will listen to this podcast about your field of research, what would you like to say? 

00:11:36 Tessa 

I think maybe I'll say something a bit more generalized to people who are doing research, like graduate students or just starting off, but progress takes time. When I first started this project, I'd never done this type of like large data analysis and it was honestly really overwhelming. And it felt almost impossible to kind of know where to even start. And what really helped me was kind of taking a step back, focusing on the bigger picture, and then breaking the work into kind of smaller and more manageable pieces. And taking things one step at a time made it a lot more manageable and kind of easier to take it all in. So that mindset has really stuck with me throughout this project, that progress does not happen all at once and that's okay. When you go from undergrad to a graduate degree, you kind of expect everything to just go the way you want it to go, but it's not always linear. And so it's important to kind of keep yourself grounded in that mindset. Yeah. 

00:12:33 Sabrina 

Fantastic. I think that's a great takeaway message for any of our trainees listening or considering doing graduate research. Well, thank you so much for coming on the podcast today, Tessa, and taking time to chat with us. 

00:12:44 Tessa 

Thank you so much for having me. 

00:12:48 Outro 

Thanks for joining us on the GOSH Podcast. To learn more about the Gynecologic Cancer Initiative and our podcast, make sure to check out our website at gynaecancerinitiative.ca.