Abstract 5873
Background
CNS metastases is a devastating complication of breast cancer, occurring in approximately 10%–15% of patients with metastatic breast cancer (MBC) and resulting in median survival of less than one year in historic cohorts. Biological factors that govern metastases to the brain, including the role of activating PIK3CA mutations, the most common actionable alterations in HR+/HER2- MBC, are poorly understood.
Methods
In this retrospective cohort study, we determined the cumulative incidence of brain metastasis in PIK3CA mutant and PIK3CA non-mutant HR+/HER2- MBC patients treated at the Massachusetts General Hospital and genotyped during their routine clinical care with a highly sensitive multiplexed assay for real time mutation profiling of clinical samples.
Results
In the overall cohort of 307 patients, 120 patients (39.1%) had PIK3CA mutant disease and 187 patients (60.9%) had PIK3CA non-mutant disease, comparable to previously published results. Median OS from the time of diagnosis of metastatic disease was 3.96 yrs (95% CI 3.40-4.87 yrs) for PIK3CA mutant patients and 4.43 yrs (95% CI 3.82-5.32 yrs) for PIK3CA non-mutant patients, p = 0.6. 22.44% of patients with HR+/HER2- disease developed brain metastases; 30.83% of PIK3CA mutant patients and 17.11% of PIK3CA non-mutant patients developed CNS metastases, p = 0.0049. Median time to the development of CNS disease was 8.61 yrs for PIK3CA mutant subset and not reached (NR) for PIK3CA non-mutant subset, p = 0.0086. Among patients with CNS metastases, median OS for PIK3CA mutant patients was 0.48 yrs (95% CI 0.27-0.74) and for PIK3CA non-mutant it was 1.09 yrs (95% CI 0.39-2.27), p = 0.019).
Conclusions
Brain metastases are common in HR+/HER2- MBC. This incidence of brain metastases is particularly high among patients with HR+/HER2- tumors harboring a PIK3CA mutation, where it approaches the incidence historically seen in HER2+ MBC. Early recognition of symptoms potentially related to brain metastases is important even in HR+/HER2- subtype of breast cancer. High incidence of brain metastases in PIK3CA mutant HR+/HER2- MBC warrants development of blood-brain barrier penetrant agents targeting the PI3K/AKT/mTOR pathway.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Isakoff: Advisory / Consultancy, Research grant / Funding (institution): Myriad; Advisory / Consultancy, Research grant / Funding (institution): Puma; Advisory / Consultancy, Research grant / Funding (institution): Immunomedics; Advisory / Consultancy, Research grant / Funding (institution): Mylan; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Pharmamar; Advisory / Consultancy, Research grant / Funding (institution): Abbvie; Advisory / Consultancy, Research grant / Funding (institution): OncoPep; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. A. Bardia: Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Immunomedics; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Radius Health; Advisory / Consultancy, Research grant / Funding (institution): Specturm; Advisory / Consultancy, Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Innocrin; Research grant / Funding (self): Biothernostics. P.K. Brastianos: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Bristol-Myer Squibb; Advisory / Consultancy: Genentech-Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: Lily; Advisory / Consultancy: TESARO; Advisory / Consultancy: AngioChem. D. Juric: Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): EMD Serono; Advisory / Consultancy, Research grant / Funding (institution): Syros; Advisory / Consultancy: Ipsen; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Placon Therapeutics. All other authors have declared no conflicts of interest.
Resources from the same session
5694 - Findings from a new specialist remote Counselling Service for Neuroendocrine Neoplasm (NEN) patients and family members
Presenter: Catherine Bouvier
Session: Poster Display session 2
Resources:
Abstract
4725 - Hematologic malignancies in temozolomide-treated metastatic pancreatic neuroendocrine tumors
Presenter: Nicole Balmaceda
Session: Poster Display session 2
Resources:
Abstract
5842 - Efficacy and toxicity of combination chemotherapy with cyclophosphamide, vincristine and an anthracycline in patients with metastatic extrapulmonary neuroendocrine carcinoma
Presenter: Leonidas Apostolidis
Session: Poster Display session 2
Resources:
Abstract
1543 - An Australian multi-centre experience of the use of peptide receptor radionuclide therapy for bronchial carcinoid tumours.
Presenter: Lisi Lim
Session: Poster Display session 2
Resources:
Abstract
4175 - Extra-pulmonary (EP) high grade (HG) neuroendocrine carcinoma (NEC): real-life outcomes of fifty-eight patients from a Portuguese cancer center.
Presenter: Rita Conde
Session: Poster Display session 2
Resources:
Abstract
3274 - Efficacy of immune check-point inhibitors (ICPi) in large cell neuroendocrine tumors of lung (LCNET)
Presenter: Shira Sherman
Session: Poster Display session 2
Resources:
Abstract
3534 - HORMONET: Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression
Presenter: Milton Barros
Session: Poster Display session 2
Resources:
Abstract
2137 - Clinical utility of Metabolic Tumor Volume in Papillary Thyroid Carcinoma
Presenter: Norihiko Takemoto
Session: Poster Display session 2
Resources:
Abstract
3864 - Correlation of thyroglobulin (Tg) oscillations with progression-free survival (PFS) in patients with radioactive iodine-refractory (RAI-R) differentiated thyroid carcinoma (DTC) treated with multikinase inhibitors (MKI).
Presenter: Jorge Hernando Cubero
Session: Poster Display session 2
Resources:
Abstract
2820 - Analytical validation of a thyroid cancer diagnostic method based on the relative quantification of CLDN10, HMGA2 and LAMB3 expression
Presenter: Mateus Barrosfilho
Session: Poster Display session 2
Resources:
Abstract