. 2015 Jul;12(12).
doi: 10.1038/nrclinonc.2015.123.

Precision medicine for metastatic breast cancer--limitations and solutions

Monica Arnedos 1 Cecile Vicier 2 Sherene Loi 3 Celine Lefebvre 2 Stefan Michiels 4 Herve Bonnefoi 5 Fabrice Andre 1 
  • PMID: 26196250
  •     78 References
  •     73 citations


The development of precision medicine for the management of metastatic breast cancer is an appealing concept; however, major scientific and logistical challenges hinder its implementation in the clinic. The identification of driver mutational events remains the biggest challenge, because, with the few exceptions of ER, HER2, PIK3CA and AKT1, no validated oncogenic drivers of breast cancer exist. The development of bioinformatic tools to help identify driver mutations, together with assessment of pathway activation and dependency should help resolve this issue in the future. The occurrence of secondary resistance, such as ESR1 mutations, following endocrine therapy poses a further challenge. Ultra-deep sequencing and monitoring of circulating tumour DNA (ctDNA) could permit early detection of the genetic events underlying resistance and inform on combination therapy approaches. Beside these scientific challenges, logistical and operational issues are a major limitation to the development of precision medicine. For example, the low incidence of most candidate genomic alterations hinders randomized trials, as the number of patients to be screened would be too high. We discuss these limitations and the solutions, which include scaling-up the number of patients screened for identifying a genomic alteration, the clustering of genomic alterations into pathways, and the development of personalized medicine trials.

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J R Soc Interface, 2018 Jan 26; 15(138). PMID: 29367239    Free PMC article.
Specific breast cancer prognosis-subtype distinctions based on DNA methylation patterns.
Shumei Zhang, Yihan Wang, +9 authors, Yan Zhang.
Mol Oncol, 2018 Apr 21; 12(7). PMID: 29675884    Free PMC article.
Applications of RNA Indexes for Precision Oncology in Breast Cancer.
Liming Ma, Zirui Liang, Hui Zhou, Lianghu Qu.
Genomics Proteomics Bioinformatics, 2018 May 13; 16(2). PMID: 29753129    Free PMC article.
Identifying Circulating Tumor DNA Mutation Profiles in Metastatic Breast Cancer Patients with Multiline Resistance.
Zhe-Yu Hu, Ning Xie, +18 authors, Quchang Ouyang.
EBioMedicine, 2018 May 29; 32. PMID: 29807833    Free PMC article.
Clinical significance of androgen receptor expression in triple negative breast cancer-an immunohistochemistry study.
Ya-Xuan Liu, Ke-Jing Zhang, Li-Li Tang.
Oncol Lett, 2018 May 31; 15(6). PMID: 29844843    Free PMC article.
Addressing the challenges of applying precision oncology.
Seung Ho Shin, Ann M Bode, Zigang Dong.
NPJ Precis Oncol, 2018 Jun 07; 1(1). PMID: 29872710    Free PMC article.
Organotropism: new insights into molecular mechanisms of breast cancer metastasis.
Wenjing Chen, Andrew D Hoffmann, Huiping Liu, Xia Liu.
NPJ Precis Oncol, 2018 Jun 07; 2(1). PMID: 29872722    Free PMC article.
Highly Cited. Review.
The Local Atomic Structure of Colloidal Superparamagnetic Iron Oxide Nanoparticles for Theranostics in Oncology.
Elena Kuchma, Stanislav Kubrin, Alexander Soldatov.
Biomedicines, 2018 Jul 20; 6(3). PMID: 30021987    Free PMC article.
A Digital RNA Signature of Circulating Tumor Cells Predicting Early Therapeutic Response in Localized and Metastatic Breast Cancer.
Tanya T Kwan, Aditya Bardia, +15 authors, Shyamala Maheswaran.
Cancer Discov, 2018 Aug 15; 8(10). PMID: 30104333    Free PMC article.
Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells.
Shan Hu, Yingchun Xu, +2 authors, He Sun.
Exp Ther Med, 2018 Aug 18; 16(2). PMID: 30116377    Free PMC article.
Benefit of everolimus as a monotherapy for a refractory breast cancer patient bearing multiple genetic mutations in the PI3K/AKT/mTOR signaling pathway.
Yehui Shi, Wenwen Zhang, +6 authors, Jinpu Yu.
Cancer Biol Med, 2018 Sep 11; 15(3). PMID: 30197799    Free PMC article.
Could local surgery improve survival in de novo stage IV breast cancer?
Zhenchong Xiong, Guangzheng Deng, +4 authors, Xi Wang.
BMC Cancer, 2018 Sep 12; 18(1). PMID: 30200932    Free PMC article.
Expression, Clinical Significance, and Functional Prediction of MNX1 in Breast Cancer.
Tian Tian, Meng Wang, +10 authors, Zhi-Jun Dai.
Mol Ther Nucleic Acids, 2018 Oct 28; 13. PMID: 30368216    Free PMC article.
The pro-metastasis effect of circANKS1B in breast cancer.
Kaixuan Zeng, Bangshun He, +7 authors, Shukui Wang.
Mol Cancer, 2018 Nov 21; 17(1). PMID: 30454010    Free PMC article.
Highly Cited.
ESR1-Stabilizing Long Noncoding RNA TMPO-AS1 Promotes Hormone-Refractory Breast Cancer Progression.
Yuichi Mitobe, Kazuhiro Ikeda, +4 authors, Satoshi Inoue.
Mol Cell Biol, 2019 Sep 11; 39(23). PMID: 31501276    Free PMC article.
Biomarkers of response and resistance to PI3K inhibitors in estrogen receptor-positive breast cancer patients and combination therapies involving PI3K inhibitors.
M Brandão, R Caparica, D Eiger, E de Azambuja.
Ann Oncol, 2019 Dec 21; 30(Suppl_10). PMID: 31859350    Free PMC article.
PIK3CA and PTEN Genes Expressions in Breast Cancer.
Nabil Hadi Alowiri, Shaden Muawia Hanafy, Reham Abdel Haleem, Ahmed Abdellatif.
Asian Pac J Cancer Prev, 2019 Sep 27; 20(9). PMID: 31554385    Free PMC article.
Nitric Oxide and S-Nitrosylation in Cancers: Emphasis on Breast Cancer.
Deepshikha Mishra, Vaibhav Patel, Debabrata Banerjee.
Breast Cancer (Auckl), 2020 Feb 08; 14. PMID: 32030066    Free PMC article.
Whole-Exome Sequencing of Matched Primary and Metastatic Papillary Thyroid Cancer.
Tariq Masoodi, Abdul K Siraj, +8 authors, Khawla S Al-Kuraya.
Thyroid, 2019 Nov 02; 30(1). PMID: 31668133    Free PMC article.
Ductal Carcinoma in Situ Biomarkers in a Precision Medicine Era: Current and Future Molecular-Based Testing.
Kevin Shee, Kristen E Muller, +3 authors, Gregory J Tsongalis.
Am J Pathol, 2018 Nov 06; 189(5). PMID: 30385093    Free PMC article.
Breast cancer tumor histopathology, stage at presentation, and treatment in the extremes of age.
Jennifer K Plichta, Samantha M Thomas, +5 authors, Rachel A Greenup.
Breast Cancer Res Treat, 2020 Jan 26; 180(1). PMID: 31980967    Free PMC article.
Tumor Drug Penetration Measurements Could Be the Neglected Piece of the Personalized Cancer Treatment Puzzle.
Imke H Bartelink, Ella F Jones, +12 authors, Geraldine Gebhart.
Clin Pharmacol Ther, 2018 Aug 15; 106(1). PMID: 30107040    Free PMC article.
Tumor slice culture as a biologic surrogate of human cancer.
Heidi L Kenerson, Kevin M Sullivan, +10 authors, Raymond S Yeung.
Ann Transl Med, 2020 Mar 17; 8(4). PMID: 32175407    Free PMC article.
circGNB1 Facilitates Triple-Negative Breast Cancer Progression by Regulating miR-141-5p-IGF1R Axis.
Peng Liu, Yutian Zou, +5 authors, Yanan Kong.
Front Genet, 2020 Mar 21; 11. PMID: 32194644    Free PMC article.
The therapeutic response of ER+/HER2- breast cancers differs according to the molecular Basal or Luminal subtype.
François Bertucci, Pascal Finetti, Anthony Goncalves, Daniel Birnbaum.
NPJ Breast Cancer, 2020 Mar 21; 6. PMID: 32195331    Free PMC article.
OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine.
Andrés López-Cortés, César Paz-Y-Miño, +7 authors, Eduardo Tejera.
Sci Rep, 2020 Mar 27; 10(1). PMID: 32210335    Free PMC article.
Impact of breast surgery on survival of patients with stage IV breast cancer: a SEER population-based propensity score matching analysis.
Yuxiang Lin, Kaiyan Huang, +2 authors, Chuangui Song.
PeerJ, 2020 Mar 29; 8. PMID: 32219021    Free PMC article.
Probing the biological obstacles of nanomedicine with gold nanoparticles.
Bin Li, Lucas A Lane.
Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2018 Aug 08; 11(3). PMID: 30084539    Free PMC article.
Metastatic breast cancer patient perceptions of somatic tumor genomic testing.
Elizabeth J Adams, Sarah Asad, +19 authors, Daniel G Stover.
BMC Cancer, 2020 May 08; 20(1). PMID: 32375690    Free PMC article.
Computer-Aided Ligand Discovery for Estrogen Receptor Alpha.
Divya Bafna, Fuqiang Ban, +2 authors, Artem Cherkasov.
Int J Mol Sci, 2020 Jun 18; 21(12). PMID: 32545494    Free PMC article.
Teaching cross-cultural design thinking for healthcare.
Mafalda Falcão Ferreira, Julia N Savoy, Mia K Markey.
Breast, 2020 Jan 21; 50. PMID: 31958660    Free PMC article.
Clinical implications of prospective genomic profiling of metastatic breast cancer patients.
Courtney T van Geelen, Peter Savas, +11 authors, Sherene Loi.
Breast Cancer Res, 2020 Aug 20; 22(1). PMID: 32811538    Free PMC article.
CircZFR functions as a sponge of miR-578 to promote breast cancer progression by regulating HIF1A expression.
Zhuo Chen, Fang Wang, +3 authors, Xinguang Qiu.
Cancer Cell Int, 2020 Aug 25; 20. PMID: 32831653    Free PMC article.
SETER/PR: a robust 18-gene predictor for sensitivity to endocrine therapy for metastatic breast cancer.
Bruno V Sinn, Chunxiao Fu, +23 authors, W Fraser Symmans.
NPJ Breast Cancer, 2019 Jun 25; 5. PMID: 31231679    Free PMC article.
circIQCH sponges miR-145 to promote breast cancer progression by upregulating DNMT3A expression.
Yuehua Li, Baohong Jiang, +6 authors, Xiusheng He.
Aging (Albany NY), 2020 Aug 07; 12(15). PMID: 32756009    Free PMC article.
Evaluation of the HER/PI3K/AKT Family Signaling Network as a Predictive Biomarker of Pathologic Complete Response for Patients With Breast Cancer Treated With Neratinib in the I-SPY 2 TRIAL.
Julia D Wulfkuhle, Christina Yau, +16 authors, Emanuel F Petricoin.
JCO Precis Oncol, 2018 Aug 16; 2. PMID: 32914002    Free PMC article.
Engineering Precision Medicine.
Wujin Sun, Junmin Lee, +3 authors, Ali Khademhosseini.
Adv Sci (Weinh), 2019 Jan 16; 6(1). PMID: 30643715    Free PMC article.
Chemotherapy Modulates Endocrine Therapy-Related Resistance Mutations in Metastatic Breast Cancer.
Dabo Zhou, Quchang Ouyang, +6 authors, Zhe-Yu Hu.
Transl Oncol, 2019 Mar 21; 12(5). PMID: 30893632    Free PMC article.
Evaluation of the prognostic significances of γ-secretase genes in pancreatic cancer.
Yun Ho Jeon, Mihyang Ha, +6 authors, Yun Hak Kim.
Oncol Lett, 2019 Apr 05; 17(5). PMID: 30944650    Free PMC article.
Prognostic significance of EIF4G1 in patients with pancreatic ductal adenocarcinoma.
Tae Sik Goh, Mihyang Ha, +5 authors, Sae-Ock Oh.
Onco Targets Ther, 2019 May 03; 12. PMID: 31043796    Free PMC article.
Visualization of human T lymphocyte-mediated eradication of cancer cells in vivo.
Xingkang He, Xin Yin, +16 authors, Yihai Cao.
Proc Natl Acad Sci U S A, 2020 Aug 30; 117(37). PMID: 32859758    Free PMC article.
High expression of UNC5B enhances tumor proliferation, increases metastasis, and worsens prognosis in breast cancer.
Shijie Wu, Xinyue Guo, +5 authors, Yiding Chen.
Aging (Albany NY), 2020 Sep 10; 12(17). PMID: 32902412    Free PMC article.
Linking autoantigen properties to mechanisms of immunity.
J Daniel Griffin, Jimmy Y Song, +2 authors, Cory J Berkland.
Adv Drug Deliv Rev, 2020 Apr 24;. PMID: 32325104    Free PMC article.
Standardization and harmonization of distributed multi-center proteotype analysis supporting precision medicine studies.
Yue Xuan, Nicholas W Bateman, +30 authors, Thomas P Conrads.
Nat Commun, 2020 Oct 18; 11(1). PMID: 33067419    Free PMC article.
Detection of genomic alterations in breast cancer with circulating tumour DNA sequencing.
Dimitrios Kleftogiannis, Danliang Ho, +13 authors, Sarah B Ng.
Sci Rep, 2020 Oct 10; 10(1). PMID: 33033274    Free PMC article.