Removing the Tubes First - The New Frontier in Ovarian Cancer Prevention?

This session features leading experts Dr. Gillian Hanley (UBC), Dr. Janice Kwon (UBC & Chair of the National BRCA Coalition), and researcher Sabrina Lloyd Ellis, who explore the latest developments in ovarian cancer prevention. They discuss the growing interest in “removing the tubes first” (opportunistic salpingectomy) as a promising risk-reduction strategy for both high-risk and average-risk women, share emerging findings from current research, and provide updates on the TUBA-WISP-II and SoROCK clinical trials. The session also highlights key considerations around timing, surgical approaches, and insights from related focus group work.

Find the recording here.

Q & A Transcript

Participant 1: Hi. My question was just regarding the fact that you mentioned that in BRCA2 patients, it's recommended that the ovaries should be removed sometime prior to menopause due to the role of estrogen in the cancers most common in those patients. I was just wondering, like, does That kind of slightly conflicts with what I've heard previously, which is that it's generally recommended to be on HRT until the age of natural menopause. So does that, is it generally, is that also true? Like, is there a difference between, say, being on HRT versus continuing to receive estrogen naturally in terms of the role of estrogen in cancers?

Clinician: Yeah, that's a good question. So when we talk about estrogen replacement therapy, it actually doesn't provide the same amount of estrogen that was naturally being produced by the body, but there is fairly substantial evidence that individuals who have their ovaries removed before the age of 50 have a decreased risk of breast cancer and that's true for the general population and it appears to be true for those who have a BRCA2 mutation, which makes sense because those who have a BRCA2 mutation are more likely to have breast cancers that individuals in the general population would get, which are predominantly estrogen receptor positive And it makes sense that those who have a BRCA1 mutation are not going to benefit as much in terms of breast cancer risk reduction because the majority of those cancers are triple negative breast cancers, meaning estrogen receptor negative, progesterone receptor negative, HER2 negative. So if they don't have those receptors, they're not likely going to respond to any changes in estrogen. I'm not sure that's answered.

Participant 1: Yeah, I guess kind of like the slight follow-up question is that when looking at the role of removing ovaries in BRCA2 patients and the role that plays in preventing breast cancer, do they also look at whether these patients were put on HRT after oophorectomy?

Clinician: Yeah, that's a good question. I think there is, I mean, the data are a little bit conflicting for BRCA2 because you will find some studies that don't find a reduction in breast cancer risk while others do and they are all going to be a little bit different in terms of you know whether they have information about patients using hormone replacement therapy or not. I think for us, the major reason for recommending that the ovaries be removed is because of that residual cancer risk in the ovary. Because although the majority of the cancers arise in the fallopian tube, we still believe that the ovary is still at risk in these individuals. And that is the primary reason why we're recommending that the ovaries be removed. I'd like to think that there is a secondary benefit, particularly for those with a BRCA2.

Participant 1: Okay, great. Thank you.

Host: Thank you for your question. And then I see that Anna also has her hand up. And I do have some questions in the chat, so I'll work on getting those together once we address this question here. Anna, you can go ahead.

Participant 2: Hi. I actually asked in the chat, but I'm going to just repeat here. So is hormone replacement therapy safe for someone with history of breast cancer and BRAC1 mutation? Because in this case, like I already had breast cancer and my oncologist told me I wouldn't be a candidate for that. And I had triple negative actually. So yeah, I'm really into joining the trial because I don't want to lose my ovaries at age 35. Yeah, so I would like to know about this, the hormone replacement therapy, because I know I'm going to have to remove the overs at some point.

Clinician: Yeah, so if you've had a triple negative breast cancer, so I mean, to me, intuitively, going on a short trial of estrogen or hormone replacement therapy shouldn't affect your prognosis from the breast cancer. We do know from studies such as the PROSE study in which individuals with the, you know, history of breast cancer or BRCA mutation had a short trial of hormone replacement therapy. We didn't see any increase in the risk of recurrence or new breast cancers in those individuals when hormone replacement therapy was taken for up to three years. I think, you know, it warrants discussion. I have encountered patients whose quality of life is terrible after having their ovaries removed and they're desperate to have something that will at least help them sleep at night and they're willing to take accept that risk of whatever that risk is and use the hormone replacement therapy to alleviate some of those those terrible symptoms that they're experiencing from the premature menopause. I know in general the breast oncologists are not keen they're not happy with any sort of hormone replacement therapy irrespective of anything. whether it's a triple negative versus estrogen receptor positive. I think it's fair to say that if you've had a mastectomy with reconstruction, then it should be safe to go on estrogen replacement therapy when there's no longer any tissue at risk.

Participant 2: Okay. Yeah, I had barotelomastectomy. Yeah, that's great. Thank you. Can I ask you just one more question? It might be silly, but...Would you consider removing just one ovary? Would this be a possibility, like removing fallopian tubes and one ovary and then keep one?

Clinician: Yeah, that's a good question. The issue is that if there was going to be a fallopian tube or ovarian cancer that was destined to occur, we don't know what side it would be on. So I'm a little bit reluctant to recommend removal of only one ovary or one fallopian tube. I think it has to be both fallopian tubes and both ovaries. But I do think that removing both fallopian tubes is a good compromise. I think that's better than removing one ovary and one fallopian tube.

Participant 2: Thank you.

Host: Wonderful questions. So we do have some comments in the chat. So I'm just going to shift our focus there for a moment and then Kendall, I see your hand will come back to you in a moment. So one in the chat was, I am 37 and considering having another baby in the next year. If that happens, I'm considering getting my tubes removed at the time of C-section. I would like to participate in the trial, but I am assuming I would not be able to if I was pregnant.

Clinician: Yeah, that's a great question. Um, We haven't encountered that situation, but I mean, depending on where you live, would it be possible to coordinate something in Vancouver? I don't know if that's a possibility. Victoria? I'm not sure. If it was possible to be able to coordinate the delivery and the self-injectomy in Vancouver, then definitely you could participate in the trial. But if it couldn't be done that way, then you'd be participating off trial. And so the only concern with that would be the follow-up, because it wouldn't necessarily be the same as those who are currently enrolled in one of those two clinical trials.

Host: Thank you. And I'm seeing a follow up for that in the chat, but I think it was addressed. So if that was your question, and it wasn't quite what you wanted as that second answer, you can go ahead and just re-queue it again. There's another question mentioning that they have the BRCA1 mutation and live in a small town in northern BC. I turned 40 this year and I'm considering doing the bilateral salvingectomy first and a bilateral oophorectomy later. Do I need my family doctor to send a referral to a gynecologist in Vancouver? And where should I consider the oophorectomy?

Clinician: Great question. So if you're considering participating in the trial, then please have your primary health care provider send a referral. They can send it to me in Vancouver and we'll arrange...to have your consultation. Well, we'll actually do first and we do this for many of our patients who are who live outside of Vancouver. We arrange an initial televisit to make sure we're all we're on the same path. and after that tele-visit consultation if you're agreeable to proceeding with the surgery then we pre-book your operation with consultation to be done within a couple of days of each other in Vancouver so if that so if that's what you're thinking about doing and we've done this for many patients who live outside of Vancouver have your primary care provider send send me a referral at BC Cancer or Vancouver General Hospital and we'll arrange the tele-visit and then the in-person consult and surgery in Vancouver. And once the surgery is done, you don't have to come back.

Host: Thank you. Another question mentions, if I understood correctly, you mentioned that a salvingectomy reduces risk of specifically high-grade serious cancer, but what about the other ovarian cancers?

Clinician: Yeah, that's a great question. So the next two most common forms of ovarian cancer are clear cell and endometrioid ovarian cancers, and they arise in uterine tissue, which ends up on the ovary. And it's believed that the fallopian tube is likely the way that that tissue gets to the ovary. So we hypothesize that salpinjectomy could reduce that risk if it's done before that tissue has had a chance to seed to the ovary. So younger ages for salpinjectomy will likely be more protective. But of course, those cancers are very rare. And so we don't have the data that we need right now to be able to show that. Um, if there is a risk reduction in endometrioid and clear cell cancers and low grade serious and mucinous cancers are, um, As far as we're aware, the fallopian tube is not really heavily involved in the origin of those even more rare forms of ovarian cancer. So high-grade serous is the most common by far, which is why we have the best data. And we know that the fallopian tube is the tissue of origin for many of these cancers and is also high-grade serous is the cancer that is associated with the BRCA pathogenic variant.

Host: Thank you. Have you modeled lifetime risk of ovarian cancer among BRCA1 and BRCA2 carriers post-BLS without the second surgery?

Clinician: Oh yeah, that's a good question. So the answer to that is no. When we did the initial model, we included the risk reduction from oophorectomy because I don't think anyone feels that cell punjectomy by itself is a safe strategy for those who have a BRCA1 or 2 mutation because we know that there are still some cancers that arise primarily in the ovary and we've seen them. Again, majority start in the fallopian tubes but we still feel that the ovary is at risk which is why we didn't model cell punjectomy by itself. I suppose it would give some risk reduction, but it will likely be inferior to the two-stage surgical procedure where the ovaries are removed. And I think also because that is still the recommendation, we don't see a lot of people who are, at least to this point, we don't see BRCA patients. pathogenic variant carriers who are only having the cell penjectomy, right? So we wouldn't have that kind of long-term data to answer that question at this point.

Host: Thank you. If a BRCA1 patient had a double mastectomy and chooses to have their ovaries removed at an earlier age, are there any risks taking hormone therapy? I thought I had heard that hormone therapy could increase the risk of uterine cancer.

Clinician: That's a good question. So I feel that if you've had a mastectomy, it should be fine to go on estrogen replacement therapy. If you still have your uterus, then you will need to be on a progestin or progesterone to protect the effects of the estrogen on the uterus. So the only reason for the progestin or progesterone is to prevent the estrogen from causing a thickening of the lining inside the uterus, which could become precancerous and ultimately cancer. So the answer to your question is yes, only if the estrogen is taken by itself. But with the progesterone, it doesn't increase the risk of uterine cancer.

Host: Thank you. So we'll pause in the chat for a moment. And Kendall, do you want to go ahead? I'm going to unmute and ask a question.

Participant 3: Can I ask a question? Can you hear? I'm a BRCA1 carrier. I have triple negative breast cancer first, so mastectomy, and then I have ovarian cancer. And then recently I have estrogen receptor breast cancer. I already have the mastectomy. So I have taken all the treatment. I'm now taking letrozole. I have the sonadronin exit infusion too. So is there anything else that I need to plan on to do for next step? Anything else?

Clinician: Well, I'm sorry to hear that. That's a really unfortunate history with triple negative, then ovarian cancer, and then estrogen receptor positive breast cancer. I can't think of anything else that you can do. You've had, I'm assuming you've had the surgery for breast cancer, double mastectomy, and obviously you've had ovarian cancer surgery. I don't think there's anything else that we could recommend at this point. Sorry, I don't have anything else to add.

Participant 3: Yeah, any more cancer because of BRCA1?

Clinician: Well, those are the main ones. It's unlikely that you're going to get another cancer that's related to your mutation. We know that those who have a BRCA2 mutation have a more generalized predisposition to other cancers like pancreas and pharynx and melanoma, but BRCA1 tends to be more specific to breast and ovarian cancer, and I'm sorry that you've had both of them.

Participant 3: So I'm done.

Clinician: I hope that's it. Yeah. I hope that's it for you.

Host: Thank you very much. Thank you. It's nice to know. Thank you for your question. Okay, Kendall, you can go ahead.

Participant 4: Okay. Thank you. I have kind of two questions here. I am age 41. I have the BRCA2 gene mutation. I was going to start with just the tube removal. Um, however, I've just been noticing more joint pain, night sweats, you know, all the perimenopause symptoms. So decided to go for, um, the tubes and ovaries being removed. Um, but I was just wondering my, um, OBGYN had mentioned the possibility of total hysterectomy. Um, when would that be advised?

Clinician: Total hysterectomy. So you've already had the ovaries and fallopian tubes removed or you're considering?

Participant 4: No, not yet. Nothing yet.

Clinician: Okay. So I think like that's an individualized decision. If you had a history of abnormal bleeding or abnormal pap smears, then it would be reasonable to consider having a hysterectomy done at the same time. But in general, for those who don't have a history of any uterine abnormalities, or cervical abnormalities, we generally don't do a hysterectomy at the time of the risk reducing surgery. I mean, there are obviously advantages and disadvantages to having a hysterectomy done at the same time. The advantages are, number one, you won't get uterine or cervical cancer, you won't have any more periods. The disadvantage is that, number one, it does prolong the operative time, but it also increases the risk of injury at the time of surgery. So there is a slightly increased risk of injury to the bladder, the ureters, which are the tubes that connect the kidneys to the bladder, a higher risk of injury to the bowel. And then there's a higher rate of infection after the operation. and the recovery is longer than just having the ovaries and fallopian tubes removed. So just having the standard laparoscopic removal of ovaries and fallopian tubes, that's a day surgery. You come into the hospital, you have the procedure done, in a couple of hours you're gone. With a hysterectomy done at the same time, you're in the hospital for one or two days, And then the recovery after hysterectomy is more like six to eight weeks, whereas for the laparoscopic surgery to remove the ovaries or fallopian tubes, it's more like three to four weeks. So for many of our, for many of my young patients who have young kids, they feel that they can't afford to take six to eight weeks to recover, especially if they have toddlers at home and they're busy. And so they generally choose just to have the laparoscopic day surgery and focus on the organs that need to be removed to prevent cancer.

Participant 4: Okay. One more kind of quick question that maybe isn't in quite the topic. I have been kind of pursuing doing mastectomy with the tram flap surgery. The concern I have is my grandmother passed away of ovarian cancer in her 50s because she went in for a hernia operation. And when she was opened up, that's when they found the cancer and it spread rapidly and within months she passed away. This was back in the nineties. So they didn't really weren't aware of her mutation and things like that. So my fears with doing like the tram flap surgery being opened up, um, like that, my risk of if there is cancer somewhere in there, will it just spread? I'm really scared about being under, under the knife, so to speak. Okay.

Clinician: Yeah, that's understandable. And we've heard patients express concern about, you know, does the cancer metastasize, you know, once it's exposed to the air? And we don't have, you know, convincing evidence that that's the case. I mean, we actually think that there's something about the biology of disease and it's coincidental that you know, the abdomen was open for whatever reason. So as far as we're aware, there isn't a significantly increased risk of metastasis of cancer when the cancer is exposed to the air.

Participant 4: Okay. It's a tough decision to make. Yeah. Okay. I appreciate that. Thank you.

Host: Thank you, Kendall. Something that has come up a few times in the chat is just wondering about how to get involved with the studies. And one of them is specifically calling out the Tubawisp 2 study.

Clinician: Yeah, how to get involved. Great. So in order to get involved, if your primary care provider can send a referral to me or anybody from my group, we would be happy to help. to evaluate you. So as long as you fit the criteria you have here within that within the age groups that are specified, you know, we would love to have you involved. And as long as you're willing to come to Vancouver to have the surgery if you don't live in Vancouver, but it's one trip. So if you're willing to do that, we would be happy to have you.

Host: Liz, hang tight. I'm going to come back to you in just a moment. Something that was brought up was wondering about the connection between osteoporosis and having the salpingo-oophorectomy.

Clinician: I just saw the note in the chat from Kristen. Hi Kristen, thanks for the note. That's a good question. I mean, it makes you wonder what your bone density level was like prior to the surgery because developing osteoporosis within a year of cell pingou phrectomy doesn't really sound plausible. I mean, I don't know how severe the osteoporosis is. So that's a little bit fast for that to happen. So I just wonder if there was a baseline bone mineral density prior to you having the surgery, because that sounds really fast. I think there was a second part to the Question as well.

Host: So I was wondering about HRT as a contributor to breast cancer.

Clinician: You're scheduled for a mastectomy February 5th. I think there's probably not much that if you're taking hormone replacement therapy now, it's not likely going to change your risk between now and And then if you're scheduled to have the surgery, for those with, you know, with a BRCA, the recommendations are either intense surveillance or consideration of double mastectomy with or without reconstruction. So I think what you're doing is totally appropriate. Hopefully that will help to relieve some distress and anxiety. Thank you.

Host: A question that we're not sure if it will be able to be answered yet, but from Jillian's research, it shows that there was an 80% cancer risk reduction in the general population. How do we think this might translate to high-risk women?

Clinician: Yeah, unfortunately, I think we really just can't say yet. And, you know, we're still getting so much more data and such a better understanding of all of these things. And, you know, the SO-ROC trial and the TUBA-WIS trial and all of these, this research is going to help us understand more about the etiology of high-grade serious cancer in people with BRCA pathogenic variants. But, you know, as has been mentioned several times, the salpinectomy alone is not recommended prevention in the high risk population. And so we're just we're just really unable to say at this point.

Host: And what is the general wait time for risk reducing salpinectomy?

Clinician: So there isn't really risk reducing self-injection alone happening yet. But so to end to get on to one of the trials is probably your best bet. And Janice will be able to give you that an indication of that.

Clinician: Yeah, it's the wait time, I think is fairly reasonable. So if I got a referral today, we could probably arrange for your surgery sometime within about a month. We do try and individualize the wait time because there are some patients who have circumstances in which they like to defer the surgery for a few months, which I think is fine. Others want to have the surgery done as soon as possible. When the surgery is laparoscopic and it's just removal of the fallopian tubes or ovaries and fallopian tubes, again, it's a day procedure. It doesn't take that much time. We can usually fit it in to our operating slate because we do other cancer surgeries, but we can usually fit these ones into the slate without too much delay. So the wait time is variable, but it's variable because of patient decision. In general, we can get our patients in within about a month.

Host: Thank you. If I've had my fallopian tubes removed, would I still or would it still be possible for me to get pregnant through IVF? So Dr. Hanley, I see that you started answering this question, but there was a comment just wondering if you had anything else to add or if you could just briefly explain that to the group we have here.

Clinician: Yeah, so if you have ovaries and a uterus, but no fallopian tubes, then your only option for conception for getting pregnant is IVF. And, you know, theoretically, that would be possible. However, of course, we do still recommend to try to, you know, complete family before doing it, because obviously having to go to IVF does complicate things, um, including financial toxicity. Although, you know, we are moving towards covering one, one, um, one, uh, shot at IVF in the province, but I think that there's, you know, still a lot of unknowns there. And yeah, so I don't think that would be something that we would really be encouraging at this point. But we, yes, it is possible to get pregnant using IVF if you don't have fallopian tubes.

Host: Thank you. And Liz, would you like to go ahead and then we'll shift back for a few final questions as we're coming up on our time or we're at our time. But go ahead, Liz.

Participant 5: Thank you. Mine's more of a comment. So I had the risk reducing bilateral supine oophorectomy at age 42 with Diane Miller. So that was kind of cool that they did that. I think we were one of the first group, my friend and myself. That went fine. I actually was taken home on the back of the tandem, which probably isn't the best thing to do after that kind of surgery, but we didn't have a car. The time. So now at age 55, I had bilateral mastectomy. And Janice, I'm not sure if you're aware of it, but I did not have reconstruction and I feel fine about that. So just the bilateral mastectomy has worked. And again, at age 55, I now have osteoporosis. So I've started the medication. And it's been interesting because both my kids don't have the BRCA2. So it's great for me. Yeah. So it was more of a comment. Thank you.

Host: Thank you. If you have suspected endometriosis, are you at higher risk of endometrioid O.C. with BRCA1?

Clinician: Yeah. So, I mean, endometriosis is a risk factor for the two next most common forms of ovarian cancer, which are endometrioid and clear cell. And that's because uterine tissue ends up in other places in the, and one of the places that can end up is on the ovary or the, or an endometrioma can develop on the ovary, but the vast majority of people with endometriosis do not get an ovarian cancer. So yes, it is an increased risk factor, but it is not, you know, there is not a high prevalence of ovarian cancer among people with endometriosis. So, you know, about 10% of people with uteruses have endometriosis and the rate of endometriosis associated ovarian cancers is very, very, very low. So it's not by any means a very strong risk factor in that sense that having endometriosis means your likelihood of ovarian cancer is very high. It is also very rare to see an endometrioid ovarian cancer in a BRCA pathogenic variant carrier. Anything you want to add to that, Janice?

Clinician: No, I agree. It's extremely rare to see an endometrioid ovarian cancer in a BRCA1.

Clinician: So I think we're saying don't add that to your list of things to be worried about.

Host: Can you join the studies if you've already had a cell venectomy but waiting seven years for the oophorectomy?

Clinician: Unfortunately, you wouldn't be eligible for the tuba WISP or the SOLROC trial. It's too bad, but I mean, I'm happy to hear that you're still going to pursue the oophorectomy. Because I know that there are individuals out there who've had the self-injectomy that have been done by general gynecologists. And it's a little bit concerning just because I don't know what kind of counseling they're getting if they don't come to us. I don't know what kind of screening or what kind of criteria are considered there. And so I'm happy to hear that you're having the oophorectomy. That's going to give you the best protection against ovarian cancer. But unfortunately, you wouldn't qualify for the trial because we're trying to compare the two-stage versus the standard. And the two-stage has to be within the context of the clinical trial.

Host: And there was some wondering in the chat about your thoughts on ovarian facts being developed at Oxford and the cancer detection test by the University College London, the ovarian cancer test.

Clinician: I don't know much about the ovarian facts, so I can't comment on it yet. I don't know where they are in the development of that and haven't seen any you know, publications relating to efficacy of that lately. So I'm sorry I can't really comment on that.

Clinician: I think it's just really early days for both. So, you know, we just keep our fingers crossed and hope that things go well, but it'll be quite some time before we have effectiveness data for either. Okay.

Host: And just quickly before we continue, I want to check in on your availability to continue to stay. Dr. Kwan and Dr. Hanley, you can let me know if you need to run off. I've got a few more questions.

Clinician: Yeah, I can stay until the end of the questions here.

Host: Um, so I'm 37 and considering having another baby in the next year. If that happens, I'm considering getting my tubes removed at the time of C-section. I would like to participate in the trial, um, assuming that, uh, would not be able to be pregnant. And now that I'm reading this question out, we might've answered a similar question. Is that correct? Just to double make sure. Did we cover this?

Clinician: Yeah, that was already answered. Um, that's just because there was a comment.

Host: Ah, I see. Thank you so much. let me see where we are then okay so brca2 positive if i chose to have my fallopian tubes removed would i still need to have a mastectomy by age 40.

Clinician: uh well i think that's um that's worthy of a discussion with your with a breast surgeon oh you've already consulted with the breast surgeon um If you have your fallopian tubes removed, I think the decision to have the mastectomy is somewhat independent of having the fallopian tubes removed. I think when the timing is right for you to have the mastectomy, then you should have it done. But I don't think the salpingectomy timing should influence when the mastectomy is done.

Host: Okay. And so that comes to the end of our questions everyone. So I'm just going to pause the recording.