The incidence of discordant clinical and genomic risk in patients with invasive lobular or ductal carcinoma of the breast: a National Cancer Database Study

Mary Kathryn Abel^{1

2}, Amy M Shui³, Michelle Melisko⁴, A Jo Chien⁴, Emi J Yoshida⁵, Elizabeth M Lancaster², Laura Van 't Veer⁶, Laura J Esserman², Rita A Mukhtar⁷

Affiliations

¹ University of California, San Francisco School of Medicine, 533 Parnassus Avenue, San Francisco, CA, 94143, USA.
² Department of Surgery, University of California, San Francisco, 400 Parnassus Avenue, San Francisco, CA, 94143, USA.
³ Department of Epidemiology & Biostatistics, University of California, San Francisco, 550 16th Street, San Francisco, CA, 94158, USA.
⁴ Division of Hematology and Oncology, University of California, San Francisco, 400 Parnassus Avenue, San Francisco, CA, 94143, USA.
⁵ Department of Radiation Oncology, University of California, San Francisco, 1600 Divisadero Street, San Francisco, CA, 94115, USA.
⁶ Helen Diller Comprehensive Cancer Center, University of California, San Francisco, 1600 Divisadero Street, San Francisco, CA, 94115, USA.
⁷ Department of Surgery, University of California, San Francisco, 400 Parnassus Avenue, San Francisco, CA, 94143, USA. rita.mukhtar@ucsf.edu.

PMID: 34934058
PMCID: PMC8692497
DOI: 10.1038/s41523-021-00366-x

The incidence of discordant clinical and genomic risk in patients with invasive lobular or ductal carcinoma of the breast: a National Cancer Database Study

Mary Kathryn Abel et al. NPJ Breast Cancer. 2021.

. 2021 Dec 21;7(1):156.

doi: 10.1038/s41523-021-00366-x.

Authors

Mary Kathryn Abel^{1

2}, Amy M Shui³, Michelle Melisko⁴, A Jo Chien⁴, Emi J Yoshida⁵, Elizabeth M Lancaster², Laura Van 't Veer⁶, Laura J Esserman², Rita A Mukhtar⁷

Affiliations

¹ University of California, San Francisco School of Medicine, 533 Parnassus Avenue, San Francisco, CA, 94143, USA.
² Department of Surgery, University of California, San Francisco, 400 Parnassus Avenue, San Francisco, CA, 94143, USA.
³ Department of Epidemiology & Biostatistics, University of California, San Francisco, 550 16th Street, San Francisco, CA, 94158, USA.
⁴ Division of Hematology and Oncology, University of California, San Francisco, 400 Parnassus Avenue, San Francisco, CA, 94143, USA.
⁵ Department of Radiation Oncology, University of California, San Francisco, 1600 Divisadero Street, San Francisco, CA, 94115, USA.
⁶ Helen Diller Comprehensive Cancer Center, University of California, San Francisco, 1600 Divisadero Street, San Francisco, CA, 94115, USA.
⁷ Department of Surgery, University of California, San Francisco, 400 Parnassus Avenue, San Francisco, CA, 94143, USA. rita.mukhtar@ucsf.edu.

PMID: 34934058
PMCID: PMC8692497
DOI: 10.1038/s41523-021-00366-x

Abstract

When molecular testing classifies breast tumors as low risk but clinical risk is high, the optimal management strategy is unknown. One group of patients who may be more likely to have such discordant risk are those with invasive lobular carcinoma of the breast. We sought to examine whether patients with invasive lobular carcinoma are more likely to have clinical high/genomic low-risk tumors compared to those with invasive ductal carcinoma, and to evaluate the impact on receipt of chemotherapy and overall survival. We conducted a cohort study using the National Cancer Database from 2010-2016. Patients with hormone receptor positive, HER2 negative, stage I-III breast cancer who underwent 70-gene signature testing were included. We evaluated the proportion of patients with discordant clinical and genomic risk by histology using Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models with and without propensity score matching. A total of 7399 patients (1497 with invasive lobular carcinoma [20.2%]) were identified. Patients with invasive lobular carcinoma were significantly more likely to fall into a discordant risk category compared to those with invasive ductal carcinoma (46.8% versus 37.1%, p < 0.001), especially in the clinical high/genomic low risk subgroup (35.6% versus 19.2%, p < 0.001). In unadjusted analysis of the clinical high/genomic low-risk cohort who received chemotherapy, invasive ductal carcinoma patients had significantly improved overall survival compared to those with invasive lobular carcinoma (p = 0.02). These findings suggest that current tools for stratifying clinical and genomic risk could be improved for those with invasive lobular carcinoma to better tailor treatment selection.

PubMed Disclaimer

Conflict of interest statement

M.M. receives research funding from Astra Zeneca, Novartis, KCRN Research, and Puma and consulting fees from Biotheranostics. A.J.C. receives research funding from Merck, Puma, Amgen, and Seattle Genetics. L.J.E. is an unpaid member of the board of directors of Quantum Leap Healthcare Collaborative and receives research funding from QLHC for the I-SPY TRIAL. She is a member of the Blue Cross/Blue Shield Medical Advisory Panel and receives honoraria and travel funding. She has a grant from Merck for an Investigator initiated trial of DCIS. L.V.T.V. is a co-inventor of the MammaPrint signature and a co-founder and stockholder in Agendia, Inc. The rest of the authors declare no competing interests.

Figures

**Fig. 1. CONSORT diagram for study population.**
NCDB National Cancer Database, ER estrogen receptor, HER2 human epidermal growth factor receptor 2.

**Fig. 2. Survival plots by chemotherapy status, clinical/genomic risk subgroup, and histology.**
Survival plots by chemotherapy status in the clinical low/genomic high-risk subgroup and clinical high/genomic low-risk subgroup (A), in the clinical low/genomic high-risk subgroup by histology (B), and in the clinical high/genomic low-risk subgroups by histology (C).

See this image and copyright information in PMC

References

1. Van’t Veer LJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530–536. doi: 10.1038/415530a. - DOI - PubMed
1. Paik S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J. Clin. Oncol. 2006;24:3726–3734. doi: 10.1200/JCO.2005.04.7985. - DOI - PubMed
1. van de Vijver MJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N. Engl. J. Med. 2002;347:1999–2009. doi: 10.1056/nejmoa021967. - DOI - PubMed
1. Cardoso F, et al. 70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N. Engl. J. Med. 2016;375:717–729. doi: 10.1056/NEJMoa1602253. - DOI - PubMed
1. Cardoso F. et al. MINDACT: long-term results of the large prospective trial testing the 70-gene signature MammaPrint as guidance for adjuvant chemotherapy in breast cancer patients. J. Clin. Oncol.506 (2020). 10.1200/jco.2020.38.15_suppl.506

Grants and funding

LinkOut - more resources

Full Text Sources
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

The incidence of discordant clinical and genomic risk in patients with invasive lobular or ductal carcinoma of the breast: a National Cancer Database Study

Affiliations

The incidence of discordant clinical and genomic risk in patients with invasive lobular or ductal carcinoma of the breast: a National Cancer Database Study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous