Dr. Ingrid Mayer, the Co-Leader of the Breast Cancer Research Program at Vanderbilt-Ingram Cancer Center, discusses her topic from the 2020 San Antonio Breast Cancer Symposium.
Welcome to Breaking Boundaries in Breast Cancer on ReachMD, sponsored by Lilly. On this program, we’ll hear from Dr. Ingrid Mayer, Professor of Medicine and Co-Leader for the VICC Breast Cancer Research Program at Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center. Dr. Mayer is here to share some advancements in early breast cancer that were featured at the 2020 San Antonio Breast Cancer Symposium. Let’s hear from her now.
The management of estrogen-positive metastatic breast cancer in this day and age has become a lot more complicated than in the olden days when we just used endocrine therapy sequentially, where first-, second-, and third-line typically were endocrine therapy monotherapy, and then patients would typically transition to chemotherapy. Nowadays, we have several other targeted treatments that are being added to monotherapy endocrine therapy, and notably the CDK4/6 inhibitors have made it big in first-line thanks to an incredible advantage in progression-free survival. There’s no particular subgroup that doesn’t benefit from the addition of CDK4/6 inhibitors in first- or second-line. There’s no biomarkers other than ER and/or PR positivity that helps these patients, but one important thing that has changed over the past year is the ability to do tumor profiling where we may find actionable alterations in the tumor, such as PIK3CA mutations, ESR1 mutations, or even BRCA mutations that may not be germline that are all actionable in the metastatic setting. Therefore, once patients progress in their first line of treatment that could be either endocrine therapy monotherapy still or endocrine therapy with a CDK4/6 inhibitor, as I said, either in first- or second-line, at that point the tumor profile may come in handy in terms of choosing not only the endocrine therapy of choice, which in the case of patients having an ESR1 mutation in the tumor, Faslodex or fulvestrant should be the drug of choice because, these mutations confer resistance to both tamoxifen and aromatase inhibitors, but also if a PIK3CA mutation is found, which is present in up to 40% of the tumors, patients may be eligible to medications such as alpelisib, which is a PI3 kinase inhibitor, alpha-specific PI3 kinase inhibitor, which has shown progression-free survival advantage in combination with fulvestrant in second and third-line endocrine therapy treatment for metastatic breast cancer patients. So, if a patient has received endocrine therapy monotherapy in first-line, a second-line typically consists of endocrine therapy with a CDK4/6 inhibitor, and in that case endocrine therapy typically is fulvestrant, and if a PIK3CA mutation is present, third-line would then become fulvestrant and alpelisib. If a patient has initiated treatment with an aromatase inhibitor plus a CDK4/6 inhibitor in first-line, typically your second-line would be either fulvestrant monotherapy or fulvestrant with a PI3 kinase pathway inhibitor. In case of PIK3CA mutations we would use alpelisib, and in the absence of a PIK3CA mutation, typically the addition there would be a medication such as everolimus, which is mTOR inhibitor. Post this patients then would typically transition to chemotherapy for the most part, as they would have exhausted at least two or three lines of endocrine therapy, either alone or in combination with targeted treatments, but there may be an opportunity to consider a PARP inhibitor for those patients that, albeit rare, may have a BRCA1 or 2 mutation in their tumor, and after exhaustion of all endocrine therapies and targeted treatments, at that point transition to chemotherapy is usually warranted. For patients that present with impressive visceral crisis from the get-go, typically we would potentially consider chemotherapy earlier in the disease trajectory, but for the most part, as most patients do benefit from endocrine therapy with or without targeted treatments, that should be preferential to bolster chemotherapy in the management of ER-positive disease in the metastatic setting in this day and age.
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