Abstract: Embodiments of the disclosure include methods and compositions related to treating an individual for HER2+ positive cancer with an appropriate treatment based on outcome of a multiparameter classifier. The methods allow for identification of HER2+ individuals that are suitable to avoid chemotherapy, in specific embodiments. Methods of the disclosure also allow for identification of HER2+ individuals that should not avoid chemotherapy. In specific embodiments, the multiparameter classifier identifies whether there is (1) a ratio of HER2 amplification, relative to a control probe, of greater than or equal to 4.5; (2) a HER2 expression level score of 3+, as determined by immunohistochemistry, in at least 90% of breast cancer cells; (3) whether there is a HER2-enriched molecular subtype; and (4) whether the individual has a wildtype PIKC3A gene.

Abstract: Osteoporosis is a common skeletal disease characterized by loss of bone mineral density (BMD) and increased risk of fracture. Osteoporosis most commonly occurs in postmenopausal women due to estrogen deficiency. We identified 3 genetic variants in steroid receptor coactivator 1 (SRC-1) that are significantly associated with a decrease in BMD in women. We characterized a functional variant in exon 18 of SRC-1 that is associated with increased loss of bone mineral density in women who received tamoxifen for treatment or prevention of breast cancer. In vitro experiments show that this variant decreases estrogen receptor alpha response (ER-alpha) to hormone, suggesting an attenuated response to endogenous and exogenous hormones in the bone of these women, and therefore a need for additional bone protective measures.

Abstract: Acquired and de novo endocrine resistance are major clinical problems in the management of breast cancer patients. Though the antiestrogen tamoxifen prolongs disease-free and overall survival in the adjuvant setting, and induces remissions in over half of the patients with estrogen receptor positive metastatic disease, all patients eventually acquire tamoxifen resistance. Furthermore, many of the resistant tumors actually appear to be stimulated by tamoxifen just as they are by estrogens. The present invention provides methods of predicting endocrine resistance comprising detecting the biological activity and/or expression of p38 MAPK and/or AIB1. The invention further provides methods of reducing, reversing, or preventing endocrine resistance comprising contacting a breast or prostate tumor with a p38 MAPK pathway inhibitor.

Abstract: Acquired and de novo endocrine resistance are major clinical problems in the management of breast cancer patients. Though the antiestrogen tamoxifen prolongs disease-free and overall survival in the adjuvant setting, and induces remissions in over half of the patients with estrogen receptor positive metastatic disease, all patients eventually acquire tamoxifen resistance. Furthermore, many of the resistant tumors actually appear to be stimulated by tamoxifen just as they are by estrogens. The present invention provides methods of predicting endocrine resistance comprising detecting the biological activity and/or expression of p38 MAPK and/or AIB1. The invention further provides methods of reducing, reversing, or preventing endocrine resistance comprising contacting a breast or prostate tumor with a p38 MAPK pathway inhibitor.

Abstract: The present invention is directed to methods involving an AIB1 polypeptide. More particularly, the methods are directed to identifying an endocrine therapy-resistant patient, to providing a prognosis for disease-free survival of a cancer patient and to treating a cancer patient that is endocrine therapy-resistant.

Abstract: Acquired and de novo endocrine resistance are major clinical problems in the management of breast cancer patients. Though the antiestrogen tamoxifen prolongs disease-free and overall survival in the adjuvant setting, and induces remissions in over half of the patients with estrogen receptor positive metastatic disease, all patients eventually acquire tamoxifen resistance. Furthermore, many of the resistant tumors actually appear to be stimulated by tamoxifen just as they are by estrogens. The present invention provides methods of predicting endocrine resistance comprising detecting the biological activity and/or expression of p38 MAPK and/or AIB1. The invention further provides methods of reducing, reversing, or preventing endocrine resistance comprising contacting a breast or prostate tumor with a p38 MAPK pathway inhibitor.

Abstract: The present invention involves a method for early detection of developing tamoxifen resistance in breast cancer. Tamoxifen is the drug of choice for hormonal therapy of a first recurrence of breast cancer, but its use is associated eventually with emergence of resistant tumors. Whereas initial treatment is usually followed by tumor regression, resistant tumors may actually resume growth under continued tamoxifen treatment. Because such growth may actually be augmented by the tamoxifen, it is essential to identify the onset of resistance as early as possible so alternative therapy may be promptly instituted. Monitoring increased levels of estrogenic tamoxifen isomers or estrogenic tamoxifen metabolites signals developing resistance.

Abstract: The present invention involves a method for early detection of developing tamoxifen resistance in breast cancer. Tamoxifen is the drug of choice for hormonal therapy of a first recurrence of breast cancer, but its use is always associated eventually with emergence of resistant tumors. Whereas initial treatment is usually followed by tumor regression, resistant tumors may actually resume growth under continued tamoxifen treatment. Because such growth may actually be augmented by the tamoxifen, it is essential to identify the onset of resistance as early as possible so alternative therapy may be promptly instituted.