ASCO Daily News

Welcome to the ASCO Daily News podcast. I'm Lauren Davis, and joining me today is Dr. Larissa Korde whose research interests focus on breast cancer treatment and prevention at the National Institutes of Health. Today we're talking about breast cancer screening as it relates to bracket gene mutations. Dr. Korde, welcome to the podcast.

Thank you for having me.

We're glad you're here. Although 12% of women in the United States will develop breast cancer sometime during their lives, approximately 72% of women who inherit the BRCA1 mutation and about 69% of women who inherit the BRCA2 mutation will develop breast cancer by the age of 80. Recently the US Preventive Services Task Force expanded the recommendation of patients who should be screened for the BRCA1 and BRCA2 genetic mutation, which is associated with multiple cancer types. How did this update come about?

The US Preventive Services Task Force last presented guidelines on this topic in 2013. The recent publication in the Journal of the American Medical Association is an update, and it reviews the evidence that has come about since 2013. It's important to note that these recommendations are not actually about who should be tested for BRCA1 or 2 mutations. What the recommendations address is really who should be screened and that screening would be evaluation of family history.

So the screening with family history is designed to identify which patients should be referred for further evaluation by a provider experience in genetic counseling and testing who can then make recommendations regarding actually having a gene test. The task force recommends that primary care providers assess women with a personal or family history of breast or ovarian cancer and ovarian includes fallopian tube and peritoneal cancers. And they also recommend that those who have an ancestry associated with a BRCA1 or 2 mutation should be assessed using a family history assessment tool.

There are a number of brief assessment tools that can be used in the clinic setting and are designed to assist providers in identifying which patients should be referred for genetic counseling and then if appropriate for genetic testing. Also the task force recommends against routine assessment and referral in patients that do not meet their set criteria.

The important update is that compared to the 2013 guideline, the population for whom risk assessment is deemed appropriate is broader, and specifically it's been expanded to include those women with a personal history of breast or ovarian cancer and those with a specific ancestry. The ancestry part of this was met to increase awareness of the strong association between BRCA1 and 2 mutations in Ashkenazi Jewish ancestry. Again, though, this is not a blanket recommendation that all women of Ashkenazi Jewish ancestry should be tested for BRCA1 and 2 mutations, just that the knowledge of ancestry should consider-- that should trigger additional evaluation.

There are certainly schools of thought that a more inclusive approach is needed. For example, there are folks who advocate for universal mutation testing in all women with breast cancer or all women with Ashkenazi Jewish descent while others favor a more targeted approach. These recommendations call for the more targeted and step-wise approach.

So the first step would be evaluation of personal and family history and ancestry followed by referral of patients that meet a certain threshold of risk. And then finally followed by testing if it's appropriate after counsel.

That's great. Sounds like it's a lot more about finding out who really needs to be tested and not so much about the test itself. So how can this update improve outcomes for patients?

Well, I think the basic goal here is that if we can do a better job at identifying who to screen for the BRCA1 and 2 mutation, then we can do a better job of offering appropriate interventions to those who take the test and test positive. And that can take many forms. The most obvious here is that those who have the highest likelihood of having the BRCA mutation will be referred for the appropriate counseling, and then they can make the decision with the advice of their providers about whether or not to undergo testing.

And, of course, there are also downstream effects. Once a patient is identified as having a BRCA mutation, she can be offered preventive interventions such as prophylactic mastectomy or [INAUDIBLE], and she can be offered more intensive cancer screening. It's important to note here that the recommendations were expanded to include women with a personal history of cancer because we know that these women are at risk for developing a second cancer. And that's important information, particularly for a patient whose original cancer was treated with curative intent.

Something that was outside of the scope of this guideline but which I think is becoming increas...

Mary Lopresti, DO, is a hematologist oncologist with the Lifespan Cancer Institute, where she treats patients who have breast and gynecologic cancers. Most of her patients are younger than 42 years. 

Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. Mary Lopresti, a hematologist/oncologist with the Lifespan Cancer Institute, where she treats patients who have breast and gynecologic cancers. Most of her patients are younger than 42 years. Dr. Lopresti, welcome to the podcast.
Oh, thank you so much, Lauren, for having me today.

We're glad you're here. Today we're talking about issues around fertility and how cancer can present challenges to women who want to be able to get pregnant and grow their families. Because you treat younger patients, at what point in the diagnosis process do you mention fertility options such as egg freezing?

Well, we've made it our practice at Lifespan to discuss this at the first touch point with the patient. So our young women who are newly diagnosed with breast cancer will come in to a multidisciplinary clinic, and so they'll need a breast surgeon, medical oncologist, radiation oncologist. And besides from talking about their new diagnosis and management, at that point, we'll also ask them if they plan on growing their family or having another baby or a baby. And at that point, we'll ask them if they would desire fertility preservation. And so we really from day 1 of meeting them will explore that option.

What are some of the struggles in helping patients navigate cancer care when they also have to decide whether or not they want to preserve their fertility?

I think this biggest struggle is timing, trying to help this woman decide on her breast surgical options, discuss genetic testing. And many of these young women have aggressive breast cancers requiring chemotherapy, so it's the timing of when we give the chemotherapy. And then if we are planning to give chemotherapy, how does fertility fit in?

Many times, I think physicians shy away from mentioning fertility because there's a delay in chemotherapy, which is so important. And so we've tried to get that timing down a little bit better by developing an algorithm to get that woman to a fertility specialized in a streamlined manner, and that has helped us navigate these young women a little bit better.

What advice do you have for physicians who ideally would mention fertility preservation but sometimes leave it out because of the patient's need to start treatment such as chemotherapy as you mentioned immediately?

Well, I think that it's very understandable for an oncologist to feel like they need to leave it out if a young woman has large tumor burden and they're very worried about starting systemic therapy. But yet, I think it's really up to us as physicians to make sure that the patient has informed consent. And ASCO has published guidelines for preservation so that we can help educate our patients on what options that they have. And I think we need to continue to try to do that and put our own worries aside.
Are there patients for whom you do not recommend fertility preservation? And how do those conversations go?

I'd say in general, no. I think we offer it to anyone who desires to have a pregnancy in the future. Again, there's always a worry in a woman who has an estrogen positive breast cancer, a large tumor, bulky lymph node disease to recommend fertility preservation because the concern has generally been that you could stimulate very high levels of circulating estradiol level with preservation. But now with letrozole, which is an aromatase inhibitor, and tamoxifen, there are ways to decrease the estradiol level and still get mature follicles as well. So I think that we do recommend fertility preservation everyone.

And then just moreover on that point is that there was a recent study by Rodriguez-Wallberg and colleagues. It was a Swedish match cohort trial. And so they looked at women undergoing fertility preservation compared it to age match controls, and there was not an increase in the risk of recurrence with fertility preservation. So it's a generally safe and can be done in about a two-week period.
That's wonderful. What do you see for the future of cancer care in oncofertility?

I think our knowledge will continue to increase as newer drugs come on the market. I think we should all be concerned about fertility because we're not going to know how they affect fertility in the mechanisms there. So I think as physicians, we have to become more educated, and I think we're going to see more physicians talking to their patients. I think we're going to see more patients having access to educational materials or looking on social media for decision trees to help them with fertility preservation.

I think we're ...