As the 37th annual San Antonio Breast Cancer Symposium (SABCS) drew to a close, a range of intriguing clinical observations and long-awaited trial updates had made the event a valuable experience for investigators and attendees alike. Among some of the most interesting updates, in my opinion, were advancements in treatments for estrogen receptor-positive (ER-positive) breast cancer, premenopausal breast cancers and advanced breast cancers.
ER Positive Breast Cancers
Results from the FERGI trial were presented at this year’s meeting. This trial is investigating the new agent pictilisib, which belong to a new class of drugs called PI3K inhibitors that could benefit patients with advanced ER positive breast cancer who have developed resistance to tamoxifen or other antiestrogen treatments.
The investigators found that adding pictilisib to the endocrine therapy fulvestrant restored sensitivity to fulvestrant to only a modest degree. Unexpectedly, PI3K mutation status did not correlate with treatment benefit. The subset of patients who benefited the most were those who had both ER-positive AND progesterone receptor-positive breast cancers. This leaves us with the understanding that the PI3K pathway is complex and that more than one mutation is likely to be driving these cancer cells.
There are however more promising PI3 kinase inhibitors being looked at currently – hopefully providing additional treatment options to this group of patients.
Treating Premenopausal Breast Cancer
Final results from the Suppression of Ovarian Function Trial (SOFT) were also presented at SABCS 2014. Up until now, tamoxifen alone after curative surgery had been considered the standard of care for premenopausal patients.
For women who are clearly at high risk, particularly those who are under 35 years of age, ovarian suppression has been shown to provide a clinically meaningful improvement in recurrence-free survival. Specifically, the 5-year likelihood of having no breast cancer recurrence was 68% for those receiving tamoxifen alone, 79% in those on tamoxifen plus ovarian suppression, and 83% in those on an aromatase inhibitor plus ovarian suppression.
How will this change our practice? Clearly the majority of young women with high-risk breast cancers will be recommended to pursue this combined anti-estrogen therapy. Women who are 45 and older who also have high risk disease (those with large tumors or lymph node involvement, for instance) can be offered this approach following careful consideration of benefits and side effects.
Immunotherapy for Advanced Breast Cancer
One interesting abstract looked at the programmed death pathway (PD) inhibitor pembrolizumab, which is used in patients with metastatic triple-negative breast cancer. This involved breast cancer patients whose tumors had progressed following multiple prior treatments.
Overall, 19% of the patients responded, with one patient who had all measurable disease disappear. Three of the five responders had their disease controlled beyond 11 months from treatment initiation, which is impressive for this group of heavily pretreated patients. There is hope that this agent, when combined with another active agent and used early on in the patient’s treatment course, can provide the same type of benefit that we see when used in other cancer types such as melanoma and Hodgkin’s lymphoma.