Abstract
e14010Background: Since trastuzumab was introduced in 1998, her 2 targeted treatment has become the standard of care. We have a wealth of targeted treatments that have been developed over the last two decades, including monoclonal antibodies, antibody drug conjugates and oral kinase inhibitors. Treatment of these cancers has been primarily directed at the her 2 neu biology. However, many of these patients also express hormone receptor activity as an additional target. Findings from the Pertain trial, monarcHER and the Patina trials support the inclusion of endocrine therapy as part of treatment. CNS metastases develop in a large portion of metastatic her 2 neu positive breast cancer patients and finding treatments that are effective in this setting is important. CDK4/6 check point inhibitors are routinely used in hormone receptor positive metastatic breast cancer. Abemaciclib (in combination with fulvestrant and trastuzumab) is listed as a category 2B option in hormone receptor positive and her 2 neu positive breast cancer in version 4.2025 NCCN breast cancer guidelines. Neither abemaciclib or fulvestrant are currently FDA approved in her 2 neu positive breast cancer. Methods: We present a limited case series of six patients who have undergone treatment for their metastatic breast cancer that have survived during the era of expanding her 2 targeted treatment options and describe an effective treatment with her 2 targeted treatment enhanced by endocrine therapy with fulvestrant and abemaciclib. This group of patients has had extensive treatment with an average of 9 systemic treatments (5 to 14) and in 2 patients with CNS involvement with 8 and 11 prior local treatments before starting this regimen. Both patients with CNS disease have had prior fam-trastuzumab deruxtecan-nxki as well as prior Her 2 Climb style treatment. After many lines of treatment we have seen a palliative benefit, including sustained control of CNS involvement. We will present in tabular form the treatments and duration of response and demonstrate effectiveness of targeting the estrogen receptor pathway in combination with her 2 neu targeting. Results: Systemic control was seen in these 6 patients after multiple lines of treatment, local and systemic with duration of response at 4 mo, 6 mo, 6 mo, 6 mo, 20 and 31 months. Conclusions: We analyze separately patients with CNS metastases finding prolonged benefit in 2 patients for 20 and 27 months after multiple systemic and local treatments had been used and failed to control CNS disease. In one of these 2 patients leptomeningeal disease was diagnosed in 2019, progressing on intrathecal and systemic treatments as well as multiple radiation treatments before stabilizing for 20 months when treated with this regimen. The other patient has had 31 months of CNS free progression on this regimen after 10 prior CNS interventions.