Method of assessing cancer status in a breast cancer patient

8,501,483

12/937439

April 14, 2009

Described are methods for assessing recurrence status in a breast cancer patient that include assaying a biological sample from the patient for a level of a biomarker selected from such as S100β or HOX-C1I, where positive detection of one or both of the biomarkers indicates a positive recurrence status. The method can be used for prognosis of poor disease free survival in a breast cancer patient, where positive detection of one or both of the biomarkers indicates poor disease survival. The method may also be used for diagnosis of recurrence, where positive detection of circulating S100β is a diagnostic variable of recurrence. The method of diagnosis is carried out on a patient who is undergoing first line therapy and/or a patient who has had surgery to remove a primary breast tumour.

Young, Leonie (Dublin, IE); McIlroy, Marie (Dublin, IE); Hill, Arnold (Dublin, IE); O'Gaora, Peadar (Dublin, IE); Earley, Sarah (Dublin, IE); McCartan, Damian (Dublin, IE)

University College Dublin, National University of Ireland, Dublin (Dublin, IE), The Royal College of Surgeons in Ireland (Dublin, IE)

1. A method for treating breast cancer in a breast cancer patient identified as having a positive recurrence status comprising a step of treating the patient with a second line therapy comprising a step of (a) identifying the breast cancer patient having positive recurrence status by assaying a biological sample from the patient for a level of a biomarker selected from S100β or HOXC11, wherein positive detection of one or both of the markers is indicative of a positive recurrence status, wherein when the biomarker is HOXC11 positive detection means an Allred score from 3-8 for nuclear HOXC11, and when the biomarker is S100β positive detection means a level of serum S100β greater than 200pg/ml or an Allred score from 3-8 for tumor cells, and (b) administering to the breast cancer patient having a positive recurrence status a second line of therapy.

2. The method of claim 1 , wherein the positive recurrence status indicates one or more of risk of poor disease survival, risk of recurrence, risk of metastasis, and diagnosis of recurrence.

3. The method of claim 1 , wherein the second line therapy comprises administering to the breast cancer patient a tyrosine kinase inhibitor.

436/64

2005/0100933 May 2005 Erlander et al.
2009/0304697 December 2009 Paik et al.
2005/010180 February 2005

Castets et al., Molecular Brain Research, 46:208-216 (1997). “Transcriptional regulation of the human S100-beta gene.” cited by applicant
Donato et al., Biochimica et Biophysica Acta, 1793:1008-1022 (2009). “S100-beta's double life: Intracellular regulator and extracellular signal.” cited by applicant
Funahashi et al., Journal of Surgical Oncology, 68(1):25-29 (1998). “Different distributions of immunoreactive S100-alpha and S100-beta protein expression in human breast cancer.” cited by applicant
Makiyama et al., Oncology Reports, 13(4):673-679 (2005). “Aberrant expression of HOX genes in human invasive breast carcinoma.” cited by applicant
McCartan et al., European Journal of Surgical Oncology, 34(10):1197 (2008). “A role for the developmental protein HOXc11 as a mediator of endocrine resistance in breast cancer.” cited by applicant
McCartan et al., Irish Journal of Medical Science, 177(Suppl 1):S14 (2008). “The developmental protein hoxc11 mediates altered differentiation in breast cancer stem cells.” cited by applicant
Zhang et al., Journal of Cellular and Molecular Medicine, 11(2):299-306 (2007). “HOXC6 and HOXC11 increase transcription of S100 beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells.” cited by applicant

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