Abstract 3324
Background
To facilitate cancer precision medicine, breast cancer organoids have recently emerged as a useful pre-clinical model for retaining sufficient fidelity regarding histology, the transcriptome and genome. However, their potential to predict clinical treatment responses remains unclear.
Methods
We generated breast cancer organoids from breast cancer tissues and performed drug sensitivity test on these organoids based on genomic analysis data.
Results
A total of 25 fresh breast cancer tissues and biopsies from 22 patients were processed between November 2017 and February 2019. Breast cancer organoids were grown successfully from 10 out of 25 patients (40%). We performed histopathological analysis of H&E stained tissues and organoid sections and confirmed that the phenotypes of organoids matched the original histological breast cancer types. We also performed whole genome DNA sequencing (WGS) and RNA sequencing (RNA-seq) on breast cancer organoids and paired breast cancer tissues. One of these breast cancer organoids had HER2 mutations (previously shown to be an activating mutation) and retained expression of estrogen receptor (ER) and progesterone receptor (PR) (Luminal A subtype). In our previous work, we identified activating HER2 mutations (S310F D769Y V777L 778insGSP) in ER positive/HER2-amplification negative breast cancer, who had developed resistance to multi-line endocrine therapy. Two patients achieved a durable partial response (approximately 1 years) to trastuzumab combined with everolimus. We also showed that HER2 mutations were constitutively active, and T47D and MCF7 overexpressing HER2 mutations were sensitive to HER2 targeted therapies combined with everolimus. Hence, we tested the effects of trastuzumab and everolimus on this HER2-mutant breast cancer organoid in vitro and in vivo. HER2-targeted therapies combined with everolimus produced regression of the HER2-mutated organoid.
Conclusions
The breast cancer organoids may serve as a high-fidelity platform and recapitulate clinical treatment responses in personalized medicine. These data provide a strong preclinical rationale for combining HER2-targeted therapies with everolimus in HER2-mutant/ HER2-amplification negative breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3361 - Providing a nurse-led telephone intervention for patients treated with oral anticancer medication: symptom management and adherence monitoring
Presenter: Etienne Minvielle
Session: Poster Display session 3
Resources:
Abstract
3937 - Chronological evaluation of health-related quality of life and physical symptoms in postoperative pancreatic cancer patients up to 12 months
Presenter: Naoko Sato
Session: Poster Display session 3
Resources:
Abstract
5620 - Understanding the patients’ Experiences of Radiation Therapy: A Qualitative Study on Prostate Cancer Patients
Presenter: Sakarias Johansson
Session: Poster Display session 3
Resources:
Abstract
1792 - Effect of Kegel exercises on prevention of urinary and fecal incontinence in patients with prostate cancer undergoing radiotherapy
Presenter: Aydan Uravylioglu
Session: Poster Display session 3
Resources:
Abstract
2169 - The Meaning of Responsibility – a Secondary Analysis of Patients and Caregivers Calls to an Oncology Emergency Telephone
Presenter: Heidi Jacobsen
Session: Poster Display session 3
Resources:
Abstract
4587 - Cognitive function changes and Associated Factors in Patients Receiving Chemotherapy
Presenter: Elif Dil
Session: Poster Display session 3
Resources:
Abstract
1981 - Prevention of dental complications in patients with multiple myeloma (MM) receiving bisphosphonates treatment
Presenter: CESCA PUIGMARTI
Session: Poster Display session 3
Resources:
Abstract
2725 - Safety profile of oral netupitant/palonosetron in hematopoietic stem cell transplantation recipients.
Presenter: Marina Bosch - Damas
Session: Poster Display session 3
Resources:
Abstract
5112 - Symptomatic and toxicity management of cancer patients using a telephone support model led by the oncology nurse
Presenter: Gemma Simó
Session: Poster Display session 3
Resources:
Abstract
1365 - Symptom cluster of fatigue, sleep disturbance and depression and its impact on quality of life among Chinese breast cancer patients undergoing adjuvant chemotherapy: A cross-sectional study
Presenter: Xiaole HE
Session: Poster Display session 3
Resources:
Abstract