The San Antonio Breast Cancer Symposium (SABCS) is an annual event cosponsored by the AACR and UT Health San Antonio’s Mays Cancer Center. Now in its 45th year, the meeting hosts about 10,000 clinicians and scientists from all over the world and is the largest and most prestigious scientific gathering on breast cancer research. At the symposium of this year, We have the honor to interview Professor Virginia G. Kaklamani who is Co-Directors of SABCS, from Division of Hematology/Oncology, UT Health San Antonio MD Anderson Cancer Center.
Oncology Frontier: Could you please introduce the history of SABCS? What are the important impacts of SABCS on breast cancer in the past 45 years?
Dr Kaklamani: As you mentioned, this is 45 years of the Symposium that we celebrated this year. The Symposium started with 30 people in a room at one of the hotels at the airport in San Antonio, and the goal for the founders (who was mostly Dr Bill McGuire and Dr Charles Coltman) was to educate the community physicians about the latest in breast cancer research. They had a very strong program in San Antonio. They knew all the leaders in breast cancer from around the world, and they invited very big names to come to San Antonio to talk to the community oncologists. From that, the Symposium grew. In the early 2000s, we had around 3000 attendees. Now, we have around 10000 attendees from 100 countries attending the Symposium. The goal really is to understand breast cancer from prevention through early diagnosis, treatment, pathology, surgery, radiation oncology and medical oncology, and more importantly, basic translational research and clinical research. So the strength of the Symposium is that it includes all individuals who are involved in breast cancer research in one big room. The advocates were included in the Symposium around 20 years after it started because that is when advocacy started to be very important. Now, we are very proud that we have advocates in all of our sessions, and they really are a big strength of the Symposium.
Oncology Frontier: What are the highlights of this year's SABCS conference? Which studies do you think may further change clinical practices/guidelines?
Dr Kaklamani: The studies that I think will change our practice start from looking at the breast cancer index in predicting benefit from ovarian function suppression in early stage breast cancer, showing that patients with a low breast cancer index have the best benefit from ovarian suppression. There was also a wonderful study from Taiwan looking at the combination of a CDK4/6 inhibitor and endocrine therapy compared to combination chemotherapy in patients who had very aggressive metastatic breast cancer, showing that the CDK4/6 inhibitor and endocrine therapy outperformed chemotherapy, and so now, for every patient with metastatic ER-positive breast cancer we should consider the use of a CDK4/6 inhibitor. There was some wonderful data on racial differences in breast cancers, especially ER-positive disease, showing that African-American women have worse outcomes, but not necessarily because of adherence to therapy or anything else, but more because of the biology of the disease, which I think is a first step in understanding why different racial groups do differently when diagnosed with breast cancer. We had DESTINY-Breast02 presented and DESTINY-Breast03 presented, with both of these trials showing an important and significant benefit of T-DXd (trastuzumab deruxtecan) in patients with metastatic HER2-positive breast cancer. I think right now T-DXd is being positioned as a second-line therapy in metastatic HER2-positive breast cancer. We had some updates from oral SERD (selective estrogen receptor degrader) drugs, including the EMERALD trial, showing that elacestrant is superior to single-agent endocrine therapy, especially in patients who have tumors with ESR1 mutations. This is a drug that is likely going to get approved by the FDA in the next few months. A wonderful trial, the CAPItello trial, looking a capivasertib in patients with ER-positive metastatic breast cancer, showed a benefit of capivasertib compared to standard-of-care endocrine therapy. I would assume, based on this trial, the FDA will approve capivasertib as a treatment option. We had another trial which I think is extremely important, the POSITIVE trial, looking at women with ER-positive breast cancer, who after their diagnosis and after they were on endocrine therapy for anywhere between 18 to 30 months, wanted to have children, so they discontinued endocrine therapy, had children, and then restarted endocrine therapy two years later. That trial showed that those women had similar outcomes to women who did not discontinue endocrine therapy. This is extremely important for our young breast cancer patients who are on endocrine therapy, suggesting that if they want to have children and discontinue endocrine therapy, it is ok to do so.
Oncology Frontier: You are one of the PI in TAILORx trial. So what is your comment of the update 12 year event rate of TAILORx presenting on this SABCS conference?
Dr Kaklamani: This year we presented the 12-year data. Joe Sparano looked at the updated analysis and showed similar outcomes to previous years, in the sense that we know that chemotherapy did not seem to benefit patients with the intermediate oncotype score, but he went into a little more detail with his analysis based on whether women were pre-menopausal or post-menopausal and how old they were. What he was able to show was that in women under the age of 40, chemotherapy did not seem to benefit them if they had an oncotype score of 11-25. Women between the age of 41 and 50 did have a benefit, as long as they were pre-menopausal. Women who were 45-50 who were post-menopausal did not benefit. To me, the take-home messages are that chemotherapy may help younger women because it makes them post-menopausal, but it seems to really work in a patient population that is between the age of 41 and 45. In that patient population, we should consider giving chemotherapy.
Oncology Frontier: You are the PI of 3 phase EMERALD as well.Could you introduce the new endocrine therapy elacestrant, and share your comments on the results of EMERALD study?
Dr Kaklamani: EMERALD was a phase III clinical trial in women with metastatic ER-positive breast cancer. Women had been on a CDK4/6 inhibitor previously, and then their cancer had progressed. They were randomized to receive either elacestrant, an oral SERD, or standard-of-care endocrine therapy, which was either fulvestrant or an aromatase inhibitor. The trial was presented last year showing an improvement in median progression-free survival with elacestrant compared to endocrine therapy in all women and in women whose tumors had ESR1 mutations. But this year, we looked at prior therapy with CDK4/6 inhibitor, and tried to look at outcomes depending on how long that prior therapy had lasted. We showed that in women where the CDK4/6 inhibitor had lasted for at least 12 months, those women had a much more clinically meaningful improvement in outcomes with elacestrant compared to standard-of-care endocrine therapy, especially in those tumors that were ESR1-mutated. In women who had been on a CDK4/6 inhibitor for more than 12 months whose tumors were ESR1-mutated, median progression-free survival on elacestrant was 8.6 months, whereas the median progression-free survival on single agent endocrine therapy was only 2 months. The FDA is evaluating the drug and we will see whether it gets approved or not, but based on this data, I think there is a patient population, especially with ESR1 mutations and especially an endocrine-sensitive patient population, that would get a significant benefit from elacestrant.