Åke Borg
Principal investigator
Abstract P2-02-09: Breast cancer subtype distribution and circulating tumor DNA in response to neoadjuvant chemotherapy: Experiences from a preoperative cohort within SCAN-B
Author
Summary, in English
Introduction: Preoperative chemotherapy in early breast cancer increases the rate of breast preservation and provides prognostic information. In the case of residual disease, a change in subtypes may be observed. Sensitive and reproducible biomarkers predicting treatment response early during the treatment course are needed in order to better exploit the potential benefit of an individualized preoperative treatment.
Material and Methods: In an ongoing prospective study within the population-based SCAN-B project (NCT02306096), patients undergoing preoperative chemotherapy for early or locally recurrent breast cancer have been treated with iv Epirubicin and Cyclophosphamide q3w x 3 in sequence with either Docetaxel q3w x 3 or Paclitaxel q1w x 9 with a preoperative intent. HER2-positive cases also received HER2-directed treatment. At baseline, patients were staged using sentinel node biopsy for clinically node-negative patients and CT scan for cytologically confirmed node-positive cases. A clinical core needle biopsy as well as tissue from the surgical specimen was collected for determination of conventional biomarkers including ER, PgR, HER2 and Ki67. Tumor biopsies for biomolecule-extraction and RNA-sequencing were taken using ultrasound guidance and collected fresh in RNAlater at baseline, after 2 treatment cycles, as well as at surgery. Blood plasma samples were collected at baseline, after one-, three-, and six- 3w treatment cycles, and post-surgery. Using RNA-sequencing data, somatic mutations were identified in the tumor biopsies and personalized analyses for circulating tumor DNA (ctDNA) were performed. A pathological complete remission (pCR) was defined as the complete disappearance of invasive breast cancer in the breast and axilla at time of definitive surgery. Subtyping was performed using modified St Gallen criteria (2013).
Results: Thus far, 45 patients aged 24-74 years have been included, of which 34 (76 %) were clinical stage 2 and 11 (24%) were stage 3. The subtype distribution at baseline was five Luminal A-like (11 %), 21 Luminal B-like (HER2 negative) (47 %), 8 HER2-positive (18 %) and 11 Triple-negative (ductal) (24 %). The rates of pCR in 38 operated cases to date were 0/3 Luminal A-like, 3/19 Luminal B-like (HER2 negative), 2/8 HER2-positive, and 4/7 Triple-negative (overall 24 % pCR rate). One patient did not undergo surgery due to clinically progressive disease. In 25 cases with evaluable residual disease at surgery, there was a shift in the subtype in 13 (52 %), the majority of which represented a transition from Luminal B to Luminal A. No Triple-negative cases underwent a change in subtype during treatment. Results of the ctDNA analyses will be presented at the meeting.
Discussion: We have established an infrastructure allowing for an extensive evaluation of preoperative chemotherapy in early breast cancer. The goal is to develop methods to refine response-guided treatment in early breast cancer using molecular responses in the tumor as well as in the blood circulation. The patients continue to be prospectively monitored with iterative ctDNA analyses during follow-up.
Material and Methods: In an ongoing prospective study within the population-based SCAN-B project (NCT02306096), patients undergoing preoperative chemotherapy for early or locally recurrent breast cancer have been treated with iv Epirubicin and Cyclophosphamide q3w x 3 in sequence with either Docetaxel q3w x 3 or Paclitaxel q1w x 9 with a preoperative intent. HER2-positive cases also received HER2-directed treatment. At baseline, patients were staged using sentinel node biopsy for clinically node-negative patients and CT scan for cytologically confirmed node-positive cases. A clinical core needle biopsy as well as tissue from the surgical specimen was collected for determination of conventional biomarkers including ER, PgR, HER2 and Ki67. Tumor biopsies for biomolecule-extraction and RNA-sequencing were taken using ultrasound guidance and collected fresh in RNAlater at baseline, after 2 treatment cycles, as well as at surgery. Blood plasma samples were collected at baseline, after one-, three-, and six- 3w treatment cycles, and post-surgery. Using RNA-sequencing data, somatic mutations were identified in the tumor biopsies and personalized analyses for circulating tumor DNA (ctDNA) were performed. A pathological complete remission (pCR) was defined as the complete disappearance of invasive breast cancer in the breast and axilla at time of definitive surgery. Subtyping was performed using modified St Gallen criteria (2013).
Results: Thus far, 45 patients aged 24-74 years have been included, of which 34 (76 %) were clinical stage 2 and 11 (24%) were stage 3. The subtype distribution at baseline was five Luminal A-like (11 %), 21 Luminal B-like (HER2 negative) (47 %), 8 HER2-positive (18 %) and 11 Triple-negative (ductal) (24 %). The rates of pCR in 38 operated cases to date were 0/3 Luminal A-like, 3/19 Luminal B-like (HER2 negative), 2/8 HER2-positive, and 4/7 Triple-negative (overall 24 % pCR rate). One patient did not undergo surgery due to clinically progressive disease. In 25 cases with evaluable residual disease at surgery, there was a shift in the subtype in 13 (52 %), the majority of which represented a transition from Luminal B to Luminal A. No Triple-negative cases underwent a change in subtype during treatment. Results of the ctDNA analyses will be presented at the meeting.
Discussion: We have established an infrastructure allowing for an extensive evaluation of preoperative chemotherapy in early breast cancer. The goal is to develop methods to refine response-guided treatment in early breast cancer using molecular responses in the tumor as well as in the blood circulation. The patients continue to be prospectively monitored with iterative ctDNA analyses during follow-up.
Department/s
- Breastcancer-genetics
- Tumor microenvironment
- Translational Oncogenomics
- The Liquid Biopsy and Tumor Progression in Breast Cancer
- Medical Radiation Physics, Malmö
- Personalized Breast Cancer Treatment
- Clinical Sciences, Helsingborg
- Division of Translational Cancer Research
- Faculty office - The medical degree programme board
- Tumor Cell Biology
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Familial Breast Cancer
- Surgery (Lund)
- Breast Cancer Surgery
Publishing year
2018-02
Language
English
Publication/Series
Cancer research. Supplement
Volume
78
Issue
4
Links
Document type
Conference paper: abstract
Publisher
American Association for Cancer Research Inc.
Topic
- Cancer and Oncology
Conference name
San Antonio Breast Cancer Symposium, 2017
Conference date
2017-12-05 - 2017-12-09
Conference place
San Antonio, United States
Status
Published
Project
- Sweden Cancerome Analysis Network - Breast (SCAN-B): a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine
- Translational development and clinical applications of circulating tumor DNA for patient stratification, therapy guidance, and disease monitoring
Research group
- Translational Oncogenomics
- The Liquid Biopsy and Tumor Progression in Breast Cancer
- Medical Radiation Physics, Malmö
- Personalized Breast Cancer Treatment
- Tumor Cell Biology
- Familial Breast Cancer
- Breast Cancer Surgery
ISBN/ISSN/Other
- ISSN: 1538-7445