After a baseline breast tumor core biopsy, eligible women with triple negative breast cancer (ER- alpha, PR and HER-2 receptor negative) will be treated with S-equol at a dose of 50 mg twice daily for a period of about 14 days (10-21 day range). After completion of treatment, a second breast tumor sample will be obtained to compare molecular changes between the two specimens. The second pathology specimen may be from the surgical resection of the breast tumor, or a repeat core needle biopsy, if no further surgery is planned. The primary endpoint will be the absolute change in the Ki67, which is a validated marker of tumor proliferation in breast cancer. Secondary endpoints will include assessment of total ER-beta and pY36 levels as measured by immunohistochemical staining and their correlation with S-equol effects. Further treatment after surgical resection or second core needle biopsy of the tumor will be guided by tumor size, nodal status and other standard parameters, and is at the discretion of the treating physician. The Investigator hypothesizes that S-equol will cause a measurable decrease in Ki-67 in estrogen receptor beta expressing triple negative breast cancers, indicating its potential efficacy in this tumor type.
Non-inferiority of partial breast irradiation (PBI) and concurrent compared to sequential
chemotherapy with respect to acute grade 3-4 radiation toxicity.
To examine whether aging increases human mammary stem/progenitor cells (MaSC) with aberrant phenotypes and if rapamycin can reduce malignant markers and MaSC number in surgical specimens.
To compare the effect of a supervised weight loss intervention plus health education materials versus health education materials alone upon invasive disease free survival (iDFS) in overweight (BMI 27-29.9 kg/m2) and obese (BMI 30kg/m2) women diagnosed with HER-2 negative, stage II and III breast cancer.
To determine the relationship between changes in weight and iDFS, and to explore interaction between the level of clinical benefit from weight loss and the intervention.
To evaluate the effect of a supervised weight loss intervention upon:
a) Overall survival
b) Distant disease free survival
d) Body composition (as measured by waist and hip circumference)
e) Insulin Resistance Syndrome associated conditions diabetes, hospitalization for
To determine the impact of a supervised weight loss intervention on IDFS within subgroups
of women with 1) hormone receptor positive breast cancer and 2) hormone receptor negative
To determine the impact of a supervised weight loss intervention on IDFS within subgroups of 1) premenopausal women and 2) post-menopausal women.
Primary: To assess the antitumor activity of lurbinectedin (PM01183) in terms of overall response rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, in the following advanced solid tumors: small cell lung cancer (SCLC), head and neck carcinoma (H&N), neuroendocrine tumors (NETs), biliary tract carcinoma, endometrial carcinoma, BRCA 1/2-associated metastatic breast carcinoma, carcinoma of unknown primary site, germ cell tumors (GCTs), and Ewing¿s family of tumors (EFTs). Secondary: To further characterize the antitumor activity of PM01183 in terms of duration of response (DR), clinical benefit [ORR or stable disease (SD) lasting over four months (SD ¿ 4 months)], progression-free survival (PFS), and one year overall survival (1y-OS) in each cohort of advanced solid tumors. Characterize the plasma pharmacokinetics (PK) of PM01183. To conduct an exploratory pharmacogenomic (PGx) and pharmacogenetic analysis. To evaluate the safety profile of PM01183 in this patient population.