The present disclosure provides compositions and methods for the treatment of subjects having a risk of invasive breast cancer. In some embodiments, these aspects allow for the pairing of the proper treatment option for the particular subject. In some embodiments, this allows for identifying subjects who, while at risk for invasive breast cancer, will not normally respond to radiation therapy, and can instead receive an alternative therapy, such as a HER2 antibody.

The present invention relates to means and methods for determining whether a patient is in need of a PD-L1 inhibitor cotherapy. A patient is determined to be in need of the PD-L1 inhibitor cotherapy if a low or absent ER expression level and an expression level of programmed death ligand 1 (PD-L1) that is increased in comparison to a control is measured in vitro in a sample from the patient. The patient is undergoing therapy comprising a modulator of the HER2/neu (ErbB2) signaling pathway (like Trastuzumab) and a chemotherapeutic agent (like dodetaxel) or such a therapy is contemplated for the patient. Also provided herein are means and methods for treating a cancer in a cancer patient for whom therapy comprising a modulator of the HER2/neu (ErbB2) signaling pathway (like Trastuzumab) and a chemotherapeutic agent (like dodetaxel) is contemplated, wherein the patient is to receive PD-L1 inhibitor cotherapy.

Improved methods and systems for diagnosing and for treating Cushing's syndrome and Cushing's Disease are provided herein, including methods and systems for concurrently treating Cushing's syndrome and differentially diagnosing Cushing's Disease from Ectopic Cushing's Syndrome in a patient with an established diagnosis of ACTH-dependent Cushing's syndrome. Treatment methods can use glucocorticoid receptor antagonists (GRAs), which differentially affect the ratio of cortisol to ACTH levels in patients having Cushing's Disease versus patients having Ectopic Cushing's Syndrome. Methods for concurrently treating and differentially diagnosing Cushing's Disease from Ectopic Cushing's Syndrome include obtaining baseline cortisol and ACTH levels of a patient, treating the patient with a GRA according to a protocol that would typically substantially elevate cortisol levels, obtaining post-treatment cortisol and ACTH levels of the patient, determining a differential relationship between baseline cortisol and ACTH levels and post-treatment cortisol and ACTH levels and providing a positive diagnosis based on the differential relationship.

The present invention discloses a SERS-nanotag comprising gold nanoparticle, an encapsulating agent, a Raman reporter and an antibody. The present invention also discloses a diagnostic kit consisting of SERS-nanotags for identification of breast cancer biomarker selected from the group consisting of Estrogen Receptor (ER), Progesterone Receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67, simultaneously in abreast cancer tissue sample using a surface enhanced Raman scattering signature peaks. The multiplexing Raman peak pattern provides the presence of multiple biomarkers at a time in heterogeneous paraffin embedded breast cancer tissue samples with a concentration level of the SERS-nanotags by applying single laser (532 nm/633 nm/785 nm) revealing simultaneous Raman peaks for the respective biomarkers.

The present invention provides a method for determining a treatment procedure for breast cancer, a method of predicting a likelihood of success in treating breast cancer, and a method for selecting an endocrine therapy agent for treating breast cancer. In particular, methods of the present invention rely on the amount of androgen receptor (AR) and estrogen receptor (ER) in a tissue sample.

Methods for treating and differential diagnosis between ACTH-Dependent and ACTH-Independent Cushing's syndrome are disclosed, in which a glucocorticoid receptor antagonist (GRA) is administered to a Cushing's syndrome patient with a basal ACTH level less than about 25 pg/mL. If i) the patients blood ACTH and ii) the patients blood cortisol, or adrenal hormone, or adrenal pre-hormone levels rise, or if the ACTH:cortisol ratio increases, then ACTH-Dependent Cushing's syndrome is diagnosed. If those levels do not rise, or if the ACTH:cortisol ratio decreases, then ACTH-Independent Cushing's syndrome is diagnosed. In some instances, the patient is recovering from surgery to remove an ACTH secreting tumor, and the method described herein is used to determine if the tumor resection was successful or complete. The GRA may be mifepristone, or a non-steroidal GRA having a heteroaryl-ketone fused azadecalin backbone, an octahydro fused azadecalin backbone, a cyclohexyl pyrimidine backbone, or a fused azadecalin backbone.

The present invention is concerned with the detection of ligands which bind to and activate steroid hormone receptors. Specifically, the present invention provides test kits and assay methods for the selective identification of steroid hormone receptor ligands from a test sample. Importantly, the test kits and assay methods described herein are cell-free and enzyme-free, and do not require expensive-to-manufacture nuclear extracts for their performance. Instead, the test kits and assay methods described herein employ reporter constructs comprising hormone response elements, which when bound by a ligand-activated steroid hormone receptor force a change in a physical property, a mechanical property, an optical property, a photochemical property or an electrochemical property of the reporter construct. Accordingly, a measured change in a physical, mechanical, optical, photochemical or electrochemical property of the reporter construct (e.g. fluorescence read-out) may be used to determine the presence of a target ligand in a sample under investigation.

The present invention relates to means and methods for determining whether a patient is in need of a PD-L1 inhibitor cotherapy. A patient is determined to be in need of the PD-L1 inhibitor cotherapy if a low or absent ER expression level and an expression level of programmed death ligand 1 (PD-L1) that is increased in comparison to a control is measured in vitro in a sample from the patient. The patient is undergoing therapy comprising a modulator of the HER2/neu (ErbB2) signaling pathway (like Trastuzumab) and a chemotherapeutic agent (like dodetaxel) or such a therapy is contemplated for the patient. Also provided herein are means and methods for treating a cancer in a cancer patient for whom therapy comprising a modulator of the HER2/neu (ErbB2) signaling pathway (like Trastuzumab) and a chemotherapeutic agent (like dodetaxel) is contemplated, wherein the patient is to receive PD-L1 inhibitor cotherapy.

The present disclosure provides compositions and methods for the treatment of subjects having a risk of invasive breast cancer. In some embodiments, these aspects allow for the pairing of the proper treatment option for the particular subject. In some embodiments, this allows for identifying subjects who, while at risk for invasive breast cancer, will not normally respond to radiation therapy, and can instead receive an alternative therapy, such as a HER2 antibody.

An in vitro test method for early detection of endometriosis and/or uterine adenomyosis in a female patient, comprising the following steps: a) providing menstrual blood of the patient to be tested, b) determining expression of the genes ESR2 and/or CXCL12 and/or CXCR4 in comparison with at least one control sample, wherein an increased expression of one or more of the genes indicates endometriosis and/or uterine adenomyosis.