Special Ask the Expert: Your Questions from the SOFT Trial Webinar

March 18, 2015

On January 13, 2015, LBBC hosted “Digging Into the Data: Understanding the Benefits of Ovarian Suppression for Young Women,” a webinar focused on the then recently-released results of the SOFT trial. Ann Partridge MD, MPH spoke about the study, which found that blocking ovarianinfo-icon function may lower the risk of cancer returning for some young women.

After the event, Dr. Partridge took time to respond to your questions.

Remember: we cannot provide diagnoses, medical consultations or specific treatment recommendations. This service is designed for educational and informational purposes only. The information is general in nature. For specific healthcare questions or concerns, consult your healthcare providerinfo-icon because treatment varies with individual circumstances. The content is not intended in any way to substitute for professional counselinginfo-icon or medical advice.

Question: When might a woman want to consider having an oophorectomy over ovarian suppression medication? Are there differences in symptoms and sides effects between the oophorectomy and medical suppression

Dr. Partridge: The only clear difference between oophorectomyinfo-icon and ovarian suppressioninfo-icon with medication is that oophorectomy is permanent and thus irreversible. Rarely, women have a very difficult time with ovarian suppression and thus, unless there are other reasons to get the ovaries out (e.g. they are a BRCA1info-icon or carrier with high risk of ovarian cancerinfo-icon), I usually recommend women start with ovarian suppression medicineinfo-icon to make sure it is tolerated before they do something that is irreversible like oophorectomy, even if they choose to get their ovaries out down the line. Obviously, there are downsides and risks to either surgeryinfo-icon or coming in and getting a monthly shot for 5 years.

Question: If a young woman has been on tamoxifen for 1 – 3 years, or even 5 years, would a switch to ovarian suppression or exemestane plus ovarian suppression be recommended?

Dr. Partridge: In my practice, I have generally applied the SOFT results to women who otherwise fit the study requirements with regard to those who benefitted from ovarianinfo-icon function suppression (OS) who are within a few years of diagnosisinfo-icon (1 – 3 years). I think it is reasonable to add ovarian suppressioninfo-icon to tamoxifeninfo-icon and consider a switch to an aromatase inhibitorinfo-icon (AI) in those women, as tolerated, but I tend to do it over time to see how they feel. For women who are 5 years out, I discuss continuing tamoxifen if they are still premenopausalinfo-icon and have enough risk for continued therapyinfo-icon (based on the ATTOM and ATLAS trials). I have not offered OS to anyone out that far from diagnosis, given it is pretty far out and thus data are not reasonably extrapolated. Of course, if a woman does become postmenopausalinfo-icon during that time, I do switch them to an AI given the prior MA-17 study which demonstrated benefits of that strategy (switch from tamoxifen to AI at 4.5-6 years).

Question: Is there any data from the SOFT trial that indicates the optimal duration of ovarian suppression?

Dr. Partridge: In both the SOFT and TEXT trials, they treated women for 5 years with OS so that is what we are recommending based on the efficacyinfo-icon and safety data, as tolerated. There are other studies that have looked at 2 – 3 years of OS and that have shown benefits of OS. So, for women who are intolerant, either because of symptoms or because they need to move on with their lives, some OS may be better than none for those that are higher risk. I would consider offering it for a 2-3 year duration in that context.

Question: Are monthly shots the only option for administration of medical ovarian suppression?

Dr. Partridge: Monthly shots are what was used in the study, although they also allowed ovarianinfo-icon removal or radiationinfo-icon. There is a 3-month doseinfo-icon of the OS shot which I sometimes use in older women but there is a concern that the ovaries may “break through” that shot (meaning the ovaries are still working and producing estrogeninfo-icon), which is worrisome especially if a woman is on an AI rather than tamoxifeninfo-icon as we wouldn’t expect an AI to work well in a woman who is still making ovarian estrogen, because AIs lower estrogen very, very low – but only in postmenopausalinfo-icon women or those whose ovaries are fully suppressed with medication.

Question: Have there been any differences in outcomes or events between those on Lupron (leuprolide) and those on Zoladex (goserelin)?

Dr. Partridge: The TEXT and SOFT studies used triptorelin as the OS medicineinfo-icon. However, leuprolide (Lupron) and goserelininfo-icon (Zoladex) both function similarly and most of us assume it is a “Coke and Pepsi” decision (i.e., which one is available and will your insurance pay for). I am not aware of any studies comparing them.

Question: I've been on ovarian suppression and experience vaginal dryness and hot flashes. How do I deal with these side effects?

Dr. Partridge: There are a number of remedies for hot flashes and vaginal dryness. I am attaching a teaching sheet from Dana Farber’s Adult Survivorship Program which addresses these issues (menopausal symptoms in general). There are medicines that can be tried in conjunction with your treatment team if the behavioral strategies don’t work well enough for the hot flashes.

Question: Have there been any trials that studied the effects of just ovarian suppression and no tamoxifen or exemestane?

Dr. Partridge: We have known for over 100 years that ovarian suppressioninfo-icon/oophorectomyinfo-icon treats breast cancer (we didn’t know back then, but now we know that it really works in ER-info-iconpositive disease only). Subsequently, there have been numerous studies that have shown that ovarian suppression (OS) is associated with about a 30 percent risk reduction alone compared with no hormonal therapyinfo-icon.

When we learned that tamoxifeninfo-icon was association with a 50 percent risk reduction, we moved to using that primarily. The SOFT trial addressed the question about whether OS added to tamoxifen helped reduce risk, which it does in higher risk and very young (35 or younger) women, at least in terms of preventioninfo-icon of new breast cancer events. There is no clear survival advantage yet, but long-term follow-up data are awaited.