RNA Disruption Assay (RDA)-Breast Cancer Response Evaluation for Individualized Therapy

The current study aims to provide validation results of RNA Disruption Assay (RDA) as a tumour response assessment tool that uses tumour core biopsies taken starting from 35 +/- 4 days after the initiation of neoadjuvant chemotherapy.

Sex

Female

Minimum age

18 Years

Inclusion Criteria

* Women aged at least 18 years;
* Patients must be able to provide informed consent and sign the informed consent form to participate in the RDA study before any study procedures starts;
* Newly diagnosed clinical stage I, II or III breast cancer with complete surgical excision of the breast cancer after neoadjuvant therapy as the treatment goal;
* Tumour size at least 1 cm in one dimension by clinical or radiographic exam (WHO criteria);
* Must have histological confirmation of invasive breast cancer of any subtype or grade;
* Patient is scheduled for neoadjuvant chemotherapy +/- antibodies and +/- other drugs according to Standard of Care;
* Patient willing to have 2 research core needle biopsies (for RDA) taken at 2 collection timepoints during neoadjuvant chemotherapy treatment.

Exclusion Criteria

* Patient who has had prior local (i.e. surgery or radiotherapy) or systemic (i.e. endocrine or cytotoxic) therapy for the current breast cancer;
* Participation in another interventional clinical trial with concurrent treatment with experimental drugs to treat the current breast cancer during the period of neoadjuvant therapy (from diagnosis until surgery);
* Stage IV breast cancer;
* Bilateral or multicentric breast tumour;
* Prior malignant disease except curatively treated in-situ maligancies;
* Concurrent pregnancy;
* Breast feeding woman;
* Concurrent medical, psychiatric or addictive disorders that may limit the ability to give informed consent or complete the trial;
* Reasons indicating risk of poor compliance with study procedures;
* Patient not able to consent;

• BACKGROUNDParissenti AM, Guo B, Pritzker LB, Pritzker KP, Wang X, Zhu M, Shepherd LE, Trudeau ME. Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy. Breast Cancer Res Treat. 2015 Aug;153(1):135-44. doi: 10.1007/s10549-015-3498-9. Epub 2015 Jul 25. PMID 26208483
• BACKGROUNDNarendrula R, Mispel-Beyer K, Guo B, Parissenti AM, Pritzker LB, Pritzker K, Masilamani T, Wang X, Lanner C. RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines. BMC Cancer. 2016 Feb 24;16:146. doi: 10.1186/s12885-016-2197-1. PMID 26911141
• BACKGROUNDToomey S, Eustace AJ, Pritzker LB, Pritzker KP, Fay J, O'Grady A, Cummins R, Grogan L, Kennedy J, O'Connor D, Young L, Kay EW, O'Donovan N, Gallagher WM, Kalachand R, Crown J, Hennessy BT. RE: RNA Disruption Assay as a Biomarker of Pathological Complete Response in Neoadjuvant Trastuzumab-Treated Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. J Natl Cancer Inst. 2016 Jul 4;108(8):djw111. doi: 10.1093/jnci/djw111. Print 2016 Aug. No abstract available. PMID 27377904
• BACKGROUNDPritzker K, Pritzker L, Generali D, Bottini A, Cappelletti MR, Guo B, Parissenti A, Trudeau M. RNA Disruption and Drug Response in Breast Cancer Primary Systemic Therapy. J Natl Cancer Inst Monogr. 2015 May;2015(51):76-80. doi: 10.1093/jncimonographs/lgv015. PMID 26063893
• RESULTCazzaniga ME, Ademuyiwa F, Petit T, Tio J, Generali D, Ciruelos EM, Califaretti N, Poirier B, Ardizzoia A, Hoenig A, Lex B, Mouret-Reynier MA, Giesecke D, Isambert N, Masetti R, Pitre L, Wrobel D, Augereau P, Milani M, Rask S, Solbach C, Pritzker L, Noubir S, Parissenti A, Trudeau ME. Low RNA disruption during neoadjuvant chemotherapy predicts pathologic complete response absence in patients with breast cancer. JNCI Cancer Spectr. 2024 Jan 4;8(1):pkad107. doi: 10.1093/jncics/pkad107. PMID 38113421