In an interview with Targeted Oncology, Reshma Mahtani, DO, discussed the key breast cancer topics during the Miami Cancer Institute Women’s Cancer Symposium and her presentation regarding HER2-positive breast cancer .
With the treatment landscape for HER2-positive breast cancer evolving rapidly, medical meetings that allow experts to share their knowledge are the key to success in the community oncology settings. According to Reshma Mahtani, DO, the Miami Cancer Institute Women’s Cancer Symposium is one such meeting that will bring together oncologists, radiation oncologists, and oncologic surgeons from across the country.
The meeting, which was held on April 21, 2023, in Miami, Florida, featured presentations on triple negative and HER2-positive breast cancer, as well as genomic testing in early-stage breast cancer.
In an interview with Targeted Oncology™, Dr. Mahtani, Chief of Breast Medical Oncology at Miami Cancer Institute, discussed the key breast cancer topics during the Miami Cancer Institute Women’s Cancer Symposium and her presentation regarding HER2-positive breast cancer.
Can you tell us about the Miami Cancer Institute Women’s Cancer Symposium?
Dr. Mahtani: We were very excited to host the Miami Cancer Institute Women's Cancer Symposium on April 21, 2023. The program was divided into 4 sessions and 2 were breast cancer related, while the other 2 included important topics in gynecologic cancer. Focusing on the breast cancer sessions, presenters reviewed various topics that are of importance for busy clinicians in practice including guidelines around germline genetic testing with a discussion about universal testing and whether this should be considered. From a medical oncology perspective there were great lectures on early stage and metastatic triple negative breast cancer and HER2 positive disease, focusing on recent pivotal trials as well as a look ahead at novel therapies. We made it a point to ensure discussions would be multidisciplinary by including surgical and reconstructive breast surgery talks as well. Finally, a very important topic that was included in the breast session was a discussion on integrative medicine approaches which is a topic that comes up quite a bit with our patients, and I feel that was very well received.
Diving into your presentation, can you explain the evolution of HER2-positive breast cancer treatment in the past few years?
Targeting HER2 is one of our greatest success stories in oncology. We've made considerable progress in the treatment of this aggressive subtype of breast cancer in both the early stage and metastatic setting, with several approved HER2 targeted agents now available.
Mortality rates in breast cancer have fallen over the years which is great news for our patients. While much of this is certainly related to earlier detection, a lot of that progress is also linked to the development of novel therapies, specifically in the area of HER2-positive disease. We now have 8 different therapies that are approved to treat HER2-positive breast cancer, some of which are approved in both the early stage on metastatic setting. For our patients, again this is great news because it means that outcomes have dramatically improved for this type of breast cancer, which was once considered the most aggressive subtype.
Which therapies are most relevant in today's landscape, in your opinion? What outcomes are you seeing with these therapies?
In the early-stage setting patients with smaller tumors that are lymph node negative are overall doing quite well. For stage I HER2 positive breast cancer, the standard is 12 weeks of paclitaxel in combination with trastuzumab, with completion of one year of trastuzumab. We now have 10 year data that confirms this is a safe and highly effective approach for these patients. According to the final 10-year analysis, the regimen was associated with an invasive disease-free survival (iDFS) rate of 91.3% and a recurrence-free interval (RFI) of 96.3%.
For higher risk patients, we routinely offer preoperative chemotherapy in combination with dual HER2 targeted antibody therapy. For those have residual disease at the time of surgery, T-DM1 should be offered, as we know outcomes are significantly better as compared to trastuzumab. In the metastatic setting, it’s been a particularly exciting time. Many patients are doing very well for 18 months or more on first line therapy with a taxane, trastuzumab and pertuzumab. In the second line setting for many years our standard was the antibody drug conjugate (ADC) T-DM1, until recently where we saw this ADC directly compared to a newer agent, trastuzumab deruxtecan (T-DXd), which was proven to be more effective. We also have the tucatinib, capecitabine and trastuzumab regimen which is an option 2nd line and beyond, with this therapy more commonly being given in the 3rd line except in the setting of CNS metastases. For later lines of therapy there is no clear standard, but fortunately many options are available including margetuximab, and chemotherapy.
What do you have your eyes on in term of HER2-positive breast cancer research?
Despite the successes we have achieved to date, many patients ultimately have disease progression and new options for treating these individuals are urgently needed. Fortunately, there is a lot of work that continues to be done in this area. There are a number of new ADCs in development, and we have already seen significant gains with this class of therapy. Although we haven’t seen a great deal of success with immunotherapy in HER2 positive disease, I remain hopeful there may be a subset of patients who may derive benefit to this approach. I’m also very interested to see where CDK4/6 inhibitors and other agents that we routinely use for ER+/HER2- MBC can be incorporated into the treatment algorithm for patients with HER2 positive disease. I think a key point to keep in mind as these newer therapies are developed is we need a better understanding of the mechanisms of resistance to develop new strategies to overcome resistance as well as to define the best therapeutic sequence for each patient.