Quiet Threat: Lung Cancer in “Non-Smoking” Women

Forget the old narrative that lung cancer belongs only to smokers. We open the door to a different reality: a rising number of women, many in their 30s to 50s, who never smoked, face late-stage diagnoses and limited options. With Dr. John Xie from Virginia Oncology Associates, we break down the biology that sets non-smoker lung cancers apart and the practical steps that can save lives through earlier detection and smarter treatment. 
 
Dr. Xie explains how genetics, hormones, and environment intersect, with a particular focus on East Asian women who show a higher prevalence of EGFR-driven disease. A vivid case study of a 40-year-old non-smoker misdirected toward melanoma reveals how easily lung cancer hides behind atypical symptoms like vision loss, fatigue, or bone pain, and why biopsy and staging matter before assumptions take over. 
 
From there, we dive into solutions. Precision oncology has changed the map: EGFR inhibitors now extend median survival in stage four disease, and combinations with chemotherapy are pushing gains further. Early-stage detection is where cure lives, and new evidence from a study of 1,000 East Asian non-smoking women shows low-dose CT can find lung cancers at stages one to three with detection rates similar to smokers. We talk through access hurdles, how to push for imaging when symptoms persist, and the promise of pairing low-dose CT with routine mammograms to simplify screening for select women. 
 
If you or someone you love has risk factors like East Asian ancestry, a family history of lung cancer, or unexplained symptoms that won’t resolve: ask for evaluation and consider low-dose CT. 

Dr. John Xie is board-certified in medical oncology, hematology, and internal medicine. He grew up in Connecticut and studied at Columbia University, and graduated with a Bachelor of Science in Biomedical Engineering. After that, he obtained his Doctorate in Medicine from the Geisel School of Medicine at Dartmouth and finished his internal medicine residency at Tulane Medical Center. 

Dr. Xie treats patients with all types of cancer and blood disorders. He remains actively engaged in advancing the field of hematology and oncology, particularly through clinical trials. He has published peer-reviewed research in several publications, including Leukemia & Lymphoma. He has also presented at numerous conferences, including the American Society of Hematology (ASH) Annual Meeting. 

Resources:

• American Cancer Society: https://www.cancer.org/ 
• https://clinicaltrials.gov/ 
• Female Asian Nonsmoker Screening Study: https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8510 
• Stanford Study: https://med.stanford.edu/news/insights/2025/05/lung-cancer-women-mammogram-screening.html 

Thank you for listening! If you're interested in hearing more from Virginia Oncology Associates, make sure to subscribe to Cancer Care Connections on Apple Podcasts, Spotify, or anywhere podcasts are available, or listen online at cancercareconnections.buzzsprout.com.

Cancer Care Connections is the official podcast of Virginia Oncology Associates. For more information, visit us at VirginiaCancer.com. or find us on Facebook or Instagram at Virginia Oncology Associates.

Transcript

Host 0:09

Welcome to Cancer Care Connections. Today we're exploring one of the biggest misconceptions in medicine that lung cancer is a smoker's disease, with Dr. John Xie, oncologist/hematologist with Virginia Oncology Associates. A growing number of women in their 30s to 50s, who have never smoked, are being diagnosed at late stages, often after their symptoms have been misread or overlooked. In this episode, we explore: why mortality rates are so high, the biological differences that set non-smoker lung cancers apart, the blind spots and current screening guidelines, unique risks in East Asian women, the promise of precision with targeted therapies for these lung cancer cases, and new research showing that low-dose CT scans can detect early-stage cancers in non-smokers with the same accuracy as in smokers. If you or someone you love has persistent symptoms, a family history of lung cancer, or risk factors tied to ancestry, this conversation is for you.

Cheryl 1:24

He remains actively engaged in advancing the field of hematology and oncology, particularly through clinical trials. In his free time, Dr. Xie enjoys spending time on the beach with his wife and dog Boba. Dr. Xie, thanks so much for joining us today.

Dr. Xie 1:40

Thank you for having me, Cheryl. Appreciate it.

Cheryl 1:41

Yeah, great to have you here. You just moved to Hampton Roads in 2024. What do you think about the area? And in particular, what is it about oncology that you're passionate about?

Dr. Xie 1:54

Yeah, well, we're having a great time so far. I moved over here with my wife and my dog. We love the beach, so it's really a great area for us. In terms of the oncology, I feel like it is the most exciting, dynamic field in medicine right now. Everything is just advancing so rapidly. And treatments that were available, you know, 20 years ago, are so different compared to now. And some of that stuff we'll go over later in this talk. But it is really amazing kind of looking back and kind of how far we've gone already and kind of the future developments that are coming ahead.

Lung Cancer Prevalence in Women

Cheryl 2:29

That is so true that the advances are happening, and it's important to be on top of that. So we appreciate you taking the time and sharing. Let's talk about lung cancer and how common it is, especially in women.

Dr. Xie 2:42

Yeah, definitely. So lung cancer is the second most common cancer in women. There's roughly 100,000 new cases of lung cancer in women per year. The only one that sort of is more common is breast cancer. It's about 300,000 cases per year. But even though there's sort of more breast cancer cases, lung cancer actually has the highest mortality rate compared to, you know, all the other cancers. So about 20% of mortality cases in women is lung cancer. Even though there's about three times more breast cancer, overall, the mortality rate is still higher in lung cancer. So that's why I think it's an important topic to go over.

Difference in Mortality Rates: Breast Cancer vs Lung Cancer

Cheryl 3:27

Absolutely. What would you say accounts for that difference in numbers and mortality rates for lung cancer patients versus breast cancer patients?

Dr. Xie 3:38

Yeah, I think that's an excellent question. And it's something that is definitely an important question for sure. Some of the reasons for why there's a higher mortality rate is basically lung cancer is not inherently sort of more deadly compared to breast cancer, but the main issue is that it's detected at later stages. Basically, stage four, that means it's it's metastatic, it's spread to other areas. And with lung cancer, unfortunately, when we see these patients, it's already progressed to stage four or metastatic. And at that point, it's no longer curable. So there's only a finite number of time that the patients can live with metastatic cancer. And a lot of that is the screening protocols that we certainly have right now. Compared to breast cancer, we have the mammograms starting at age 40 that catch these breast cancers, usually in early stages. For lung cancer screening, we mainly have the screening for smokers, but actually 20 to 25 percent of lung cancer in women are from non-smokers. So, how do these people get screened? And the reality is right now they're not screened, and they're basically caught when they have these very atypical symptoms, such as fatigue, bone pain, when the cancer sort of spreads to the bone, and it's often found incidentally when you're looking for something else. But really, by that time, it's already stage four and metastatic, and the prognosis is definitely worse compared to the early stages.

Cheryl 5:17

You mentioned 20 to 25 percent of lung cancer in women are non-smokers. So we understand that if you're a smoker, you understand that there's definitely something predetermined, a risk of some sort. But you're saying that 20 to 25 percent of women. Oh my goodness. So it's pretty amazing. Yeah, it's gone up too. That seems to have gone up. Yeah. So let's talk about that rise, if you will, and then we'll go back to screening and some of the things related to later stage determination of this disease. But talk about that, please.

Dr. Xie 5:53

Yeah, definitely. So I think in general, lung cancer is so closely ingrained with smoking. Yes, that I think at this point everybody sort of associates, you know, lung cancer with smoking. But there's not much sort of public awareness or perception that there is this subgroup of lung cancer, especially women who are non-smokers. They've never smoked a day in their life. And usually these women are pretty young in their 30s to 50s range that are getting these lung cancers. So this can be very sad cases because you kind of find them later on. There's no screening protocols. In terms of why we're seeing more lung cancers in these non-smokers and women, there's no sort of direct explanation for why they're tied, but we have a lot of different associations. So it's definitely a combination of different sort of genetic factors, hormone factors, and environmental factors. The genetic factors, actually, in this population, we see it most commonly in East Asian women. This is in China, Japan, and Korea, where up to 60 to 70 percent of lung cancer cases are this subcategory of non-smoking, East Asian women, in their 30s to 40s. So a very high prevalence in that category. So there is definitely some genetic factors involved, even though we don't have the exact genes. The hormonal factors, there are some estrogen receptors in the lung tissue that we think interacts with some of these signaling pathways, which I'll go into later, related to this epidermal growth factor receptor or EGFR, that sort of we think drive this tumor response. And then, of course, last, there's definitely some environmental factors because as we know, smoking directly causes DNA damage and drives cancer growth. But for the non-smokers, there's some other sort of environmental stimulus that causes cell growth and proliferation, whether that's secondhand smoke, sometimes it's radon exposure. Even people who cook in these kind of stir-fry, in these hot temperature environments with the fumes, the cooking fumes, that is also associated with the increased rate. And that's very common in these East Asian cultures as well. So that might be associated as well. So it's not in like one specific thing that we've identified, but it is a combination of all these factors.

Cheryl 8:31

Wow. And and so for a population that might not even think this is an issue, there are no real current screening guidelines, are there? And you mentioned earlier, I'm a little fatigued. And that could be a symptom of many, many things. So let's kind of talk first about some of the current screening guidelines for lung cancer, if there are any, and maybe what women can kind of think about as they go to the doctor or if they're looking at their health and not feeling quite right, that kind of thing.

Current Smoking Guidelines

Dr. Xie 9:02

Yeah, definitely. So the current screening guidelines, basically that you know, we have from the American Cancer Society, are really smoking focused. So basically, anybody who's in this range of ages 50 to 80, who've had a 20-pack year history of smoking, and they're either currently smoking or smoked within the past 20 years, then they qualify for what's called low dose CT scans once a year to look for any suspicious lung nodules. Depending on the size, would either need additional screening or biopsy, kind of depends on the size and characteristics. So that is kind of the protocols we have right now. But, you know, really, if you think about it, it completely sort of misses this population of young women who are non-smokers and sort of even under 50. And it really doesn't address that population at all.

Case Study

Cheryl 9:56

No, not at all. Let's talk about some cases. I know you have a recent case that you've seen, and you mentioned earlier that age range of 30 to 50, which is again younger than the screening for women smokers. I know you have a case study you wanted to share with us that can probably shed some light more on what you see and what we should be focused on.

Dr. Xie 10:17

Yeah, definitely. So I recently had this 40-year-old female. She was a non-smoker. She actually got referred to me for evaluation of metastatic melanoma. Basically, she went to her eye doctor. She was having increasing blindness in her right eye. And then, you know, the eye doctor looked in, saw some evidence of cancer in the back of her eye, basically, diagnosed her with this uveal melanoma, which is a type of melanoma in the back of the eye. They did some scans because melanoma can really go to anywhere. And they found a three to four centimeter lung nodule in the chest. So they basically referred her to me for melanoma. For us, you know, because they didn't do any biopsies, I never assumed that this is what it is. We always have to prove it with a biopsy. So we end up biopsying the lung mass, and it shows lung cancer. So lung adenocarcinoma. And then we do some further scans with PET scans, and really there's disease kind of all over the bones at that point. And then I kind of circle back, you know, talking with the eye surgeon. It's confirmed lung cancer. Do you really feel like this is melanoma? And he said, you know, the characteristics don't really look like melanoma. He said it would be the most aggressive kind of looking melanoma I've ever seen. So I think in the end, the big picture was we do think it was the lung cancer that was the primary that spread to the eye and that caused the blindness. So this is one of those situations where, again, like I said, early age, in her 40s, non-smoker developing lung cancer, and you have these very atypical symptoms, and this time just blindness in the eye. And even in these cases, it's commonly still misdiagnosed by other specialists because nobody is thinking about lung cancer for this lady in her 40s, never smoked. So even that kind of delays the diagnosis because you're thinking about other things, other primaries. But I think it's a good illustration of what we see in the clinic because I can promise you, everybody who either specializes in lung cancer or sees kind of general cancer patients like us, we all have these kind of patients in our practice in our clinic, which is these younger women non-smokers with lung cancer.

Treatment Options-Later Stage Lung Cancer

Cheryl 12:35

What are some treatment options for women who come to you with a later stage lung cancer?

Dr. Xie 12:43

Yeah, I think that's definitely a very important question. One important thing that we see with these folks who are non-smokers is that they have a higher tendency to have targeted mutations. Like I was mentioning before, it's just a different disease biology compared to people who smoke and get cancers. Smoking causes DNA damage and leads to these other mutations, usually TP53, KRAS mutations. But for the non-smokers, they sort of have a different pathway to developing cancer. And that leads to the most common mutation that we see, which I alluded to earlier, which is the epidermal growth factor receptor or EGFR receptor mutation. And nowadays, that mutation was first discovered in the 2000s. And at that point, in the 2000s, for people who are stage four lung cancer with the current chemo that we have and we still use, the median overall affected survival was about 8 to 10 months at that time. Yeah. So that's kind of all we had. And once these EGFR sort of we call inhibitors or small molecule inhibitors were discovered in the 2000s, they've been sort of gradually updated. Right now we're sort of at the third generation of these inhibitors. But the average survival is around 38 months, a little bit more than three years, these inhibitors, which are pills that people take every day. So it wouldn't be anything, you know, they wouldn't need any chemotherapy. Although nowadays there's some trials, some data, with combining chemotherapy and these pills that would lengthen the survival to more than four years. So there's still things that are coming out and they're testing to kind of improve things. But from that perspective, it does offer an avenue in terms of treatment, in terms of prolonged survival in this subset of patients.

Cheryl 14:44

So if I'm understanding you correctly, you're saying that for younger women who are non-smokers who are diagnosed with lung cancer, typically it is an EGFR mutation.

Dr. Xie 14:56

I would say about 30 to 40% of these cases are EGFR. If they're an East Asian woman, it's probably like 70%. That's very high. Yeah.

Cheryl 15:05

Okay. And technology is working to perhaps change the prognosis a little bit, a little bit for the better. Is that what you're seeing? Some of the advances related to lengthening the time for women who have been diagnosed with this. Is that right?

Dr. Xie 15:23

Exactly. And it's all because of this different disease biology that we see. Most smokers don't have this EGFR mutation, so it's really with the non-smokers. With clinical research and trials, the oncology field has been able to find a targeted therapy that targets directly this we're called this driver mutation. That's EGFR that is sort of driving the cancer.

Cheryl 15:46

You mentioned earlier that part of the issue is it is caught so late at stage three, stage four. But if it were to be caught earlier, what are the chances for this woman?

Dr. Xie 15:58

Yeah, so basically, as long as it's stage one to three, then the goal would be curative. That's always the goal. So at that point, you're talking about a surgery to remove the mass. Sometimes if it's stage two or three and they have the EGFR, we can give that pill, which is called osimertinib, for another couple of years, two to three years, and that can lower the risk of a recurrence. But in general, if they can receive surgery, then it's curative and it's not sort of life-defining. That's the same with breast cancer because the majority of breast cancers is detected early stages, stages one, two, and three. And if they're able to have a surgery, then that's curative and the prognosis is great. So that would be the same with lung cancer if they're able to detect it early.

Cheryl 16:46

All about time, right? All about time. Let's switch now to talk about public awareness and how people in the mainstream public should be made aware of this, women in particular. What do you think some of the barriers are to raising awareness related to non-smoking women and lung cancer?

FANS Study

Dr. Xie 17:05

I think that's really an excellent question. And that's kind of the crux of kind of the whole discussion. From my perspective, it all really comes down to the stigma that's related to lung cancer in that it's a smoker's disease. Even if you ask a young woman, she's in her 40s, she has lung cancer. I think the general perception or general thought is that, wow, you must have started smoking when you were 10, you know, to get to a 30 packet history. And then she's like, no, no, no, I haven't smoked a single cigarette in my life. Even then, it's still hard to believe. How did you get this lung cancer? So I think it's just so strongly kind of ingrained in the culture that because of the stigma, there's even for the patient, kind of herself, it's hard for her to sort of speak out and raise that awareness because of that sort of scarlet letter that's there, even though it's not a true scarlet letter. Then as a result, we don't really hear about, for example, I feel like all of us have heard about the young female, 30s to 40s with breast cancer, but hardly anybody ever mentions somebody in that same category, you know, the same age non-smoker with lung cancer. I feel like nobody ever sort of brings that up. And I think a lot of it is, like I said, the culture, the public perception, the stigma. And I think that a lot of it is about raising awareness, you know, that like I said, 20 to 25% is in non-smokers. So there's a significant amount of people out there that haven't smoked that are getting lung cancer.

Cheryl 18:37

Well, it starts here, right? It starts with having conversations like these. There's a study. It's called the Female Asian Nonsmoker Screening Study. And I know you want to discuss the findings of that and the implications for expanding screening for this type of cancer. Can you talk about that?

Dr. Xie 18:56

Yeah, definitely. I think a lot of these studies are honestly kind of long overdue. And we we've known about sort of these associations for a long time with kind of younger women, East Asian and lung cancer, but they finally did this study, you know, in 2025, which is great. It definitely moves things forward. But they basically looked at 1,000 women, East Asian, non-smokers. They were ages 40 to 74. So they covered, you know, both the younger demographic and older as well. They screened these 1,000 women with the low-dose CT scan, which is what you would normally do with smokers, and they found basically 13 lung cancer cases. So 1.3% of that population were positive. All of those cases were sort of stages one to three. They were all early stage, and none of them were stage one. A couple were stage two, and the last two were stage three. All of them got surgery. Some of them, depending on the... they still got some additional EGFR pills afterwards. But all of them are still alive and as far as we know, in remission because they were detected early. So I think that is a very promising study. And actually, if you compare that study to sort of the larger smoking studies that we've seen in terms of screening, there's like 100,000 people that they've tested in smokers. The sort of the prevalence is actually around the same. It's also around that 1.1 to 1.2% of detection rate. So it's actually very similar to what they found in smokers. Of course, this is still a very small sample size. You know, it's only 1,000 people, but it's encouraging that at least the detection rate in this sort of this high-risk population is actually pretty similar to the smokers who are also high risk.

Cheryl 20:50

We spoke earlier about the guidelines and how the guidelines now are for smokers past the age of 50. If someone is listening to this, is concerned, might be in that population that is higher risk. Can they ask for a screening? Is that something that is in their power?

Dr. Xie 21:09

Yeah, I think that's a very good question. And that's something that is unfortunate, a lot of it is related to the insurance in terms of what they cover and won't cover. I think eventually they will incorporate this into the guidelines. Then that means the insurance will cover it. But as of right now, the insurance won't automatically cover it unless you have some sort of symptoms, which include cough, shortness of breath, those kind of things that would allow usually the primary care doctor to then order either a chest x-ray or the CT scan.

Cheryl 21:44

What direction do you see for lung cancer research for women in particular?

Dr. Xie 21:49

So there's a lot of new drugs coming out for EGFR. So I think that is a very exciting area of research. And there's more research involving. The EGFR inhibitors with chemotherapy, combining it with radiation, all of these have been shown to increase the amount of time that people can live and be in remission. So those are all very promising. And I think, like I said, with the screening guidelines in the future, I'm very hopeful that they can add that element to the screening such that for these women who start at 40 who get mammograms, it may be feasible to add the low dose CT together with the mammogram at the same time. So they don't need to, you know, go to get another scan at a separate time. If they can package that together in a single session, because they're getting those scans yearly for the mammograms anyway, then that would make it easier to get these things done. And it seems like from smaller studies, such as there was a Stanford study that looked into this, that it would be feasible to just couple those together as a screening mechanism. So that would be another thing worth exploring. And of course, we're always into looking to personalize medicine biomarkers, whether that's getting a blood sample or a tissue sample and seeing if certain people are higher risk for developing cancer. That's also an emerging field developing in the pipeline. I would say that in general, for these patients who have a high risk for lung cancer, whether that's because of the East Asian ancestry, they have a high family history of lung cancer, even if they're non-smokers, it's important to pay attention to the symptoms and bring it up to your primary care. I think the primary care, they can find a reason to order the CT scan. You know, it's not that big of a deal to order, to at least get some answers and to not just ignore those symptoms. I think a lot of times some of these symptoms, especially from women, are sort of brushed off or brushed away and they're not even taken seriously. So that is really the key advice that I would have for people in those high risk categories.

Resources

Cheryl 24:04

Dr. Xie, thank you so much. Before we wrap this up, wanted to know if you had any resources, any places for anyone who wanted to get more information, places that you trust that they can go and learn more about lung cancer, about treatments, things like that. I know you'll bring to us any new developments, but in the meantime, if there's any place that you trust, where would you suggest they go?

Dr. Xie 24:29

Yeah, I would say the American Cancer Society, I think is a really good resource to look into screening guidelines. If the screening guidelines do change and they update to allow the subcategory that we talked about to get screening earlier, then it would certainly be reflected in the guidelines. Of course, there's the clinicaltrials.gov. That's basically where the new trials are coming up. And then FANS study that we talked about, that is, you know, one of the studies that's ongoing. If people want to look up what are the most recent trials that are ongoing in this space, they can also find that out at the clinicaltrials.gov website for people who are interested.

Cheryl 25:09

Thank you so much for spending time with us and for making us more aware about the prevalence of lung cancer, especially in non-smoking women. We appreciate your time.

Dr. Xie 25:20

Thank you so much, Cheryl. I'm so happy to be an advocate for these patients because it's such an underrecognized population of people.

Host 25:31

Thank you for joining us today for Cancer Care Connections. If today's episode reshaped how you think about lung cancer, share it with someone who needs to hear it. Awareness is one of the most powerful tools we have, especially for women who don't fit the traditional risk profile. A special thanks to Dr. John Xie for helping us break down the science, the gaps in screening, and the actionable steps that can lead to earlier detection and better outcomes. If you have risk factors like East Asian ancestry, a family history of lung cancer, or symptoms that just don't go away, talk to your doctor and ask whether a low-dose CT scan could be appropriate for you. And if you found value in this episode, leaving a review helps more listeners discover information that could truly make a difference. Don't forget to subscribe to our podcast via Apple Podcasts, Spotify, or anywhere podcasts are available, or listen online at CancerCareConnections.buzzsprout.com. Cancer Care Connections is the official podcast of Virginia Oncology Associates. For more information, visit us at VirginiaCancer.com or find us on Facebook or Instagram at Virginia Oncology Associates.