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
5612 - Evaluation of germ line mutational status among women with triple-negative breast cancer in Russia
Presenter: Elena Shagimardanova
Session: Poster Display session 2
Resources:
Abstract
4142 - Association of derived neutrophil-to-lymphocyte ratio (dNLR) with pathological complete response (pCR) after neoadjuvant chemotherapy (CT)
Presenter: Alberto Ocaña
Session: Poster Display session 2
Resources:
Abstract
1733 - Competing nomogram for late-period breast cancer-specific death in patients with early-stage hormone receptor-positive breast cancer
Presenter: Jianfei Fu
Session: Poster Display session 2
Resources:
Abstract
1978 - A Nomogram to Predict Pathologic Complete Response of Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Based on Simple Blood Indicators
Presenter: Fanrong Zhang
Session: Poster Display session 2
Resources:
Abstract
3062 - Identification of GSTP1 transferred by extracellular vesicles responsible for adriamycin-resistance in breast cancer cells
Presenter: Sujin Yang
Session: Poster Display session 2
Resources:
Abstract
5274 - Expression of X-linked Inhibitor of Apoptosis Protein (XIAP) and its Association with Clinicopathological Parameters in Invasive Breast Cancers
Presenter: Gayathri Devi
Session: Poster Display session 2
Resources:
Abstract
1324 - The prognostic significance of preoperative tumor marker (CEA, CA15-3) elevation in breast cancer patients
Presenter: Soo Youn Bae
Session: Poster Display session 2
Resources:
Abstract
4877 - Correlation of clinical and pathological features with the tumour microenvironment in DCIS. An institutional experience
Presenter: Ann Eapen
Session: Poster Display session 2
Resources:
Abstract
2471 - Correlation between radiologic complete response (rCR) in contrast-enhanced magnetic resonance imaging (CE-MRI) after neoadjuvant chemotherapy for early breast cancer and pathologic complete response and their impact in recurrence-free survival
Presenter: Ariadna Gasol Cudos
Session: Poster Display session 2
Resources:
Abstract
2632 - Ring-like uptake appearance on dedicated breast positron emission tomography before chemotherapy predicts outcome of neoadjuvant chemotherapy in breast cancer
Presenter: Norio Masumoto
Session: Poster Display session 2
Resources:
Abstract