sequential therapies modeled on evolutionary dynamics for breast cancer

Conditions: Metastatic Breast Cancer

Summary: the purpose of the study is to test a treatment strategy with currently approved drugs to see if it is practical to administer the available drugs in a new way that researchers hope could be more effective in treating metastatic breast cancer.


Eligibility criteria:
inclusion criteria: * female patients 18 years or older * histologically or cytologically confirmed diagnosis of hormone positive her2 negative metastatic breast cancer per asco/cap criteria (allison et al, 2020, wolff et al, 2018), with diagnosis established through either a breast/axillary biopsy or biopsy of a metastatic lesion. * hormone positive mbc previously treated with endocrine therapy with either an aromatase inhibitor or tamoxifen (alone or in combination with a cdk4/6 inhibitor). * elevated breast tumor markers which may include cancer antigen 15-3 (ca 15-3) levels above the institutional upper limit of normal (uln) range of 0.0-31.0 u/ml, cancer antigen 27-29 (ca 27-29) (range \<38 u/ml) and/or elevated carcinoembryonic antigen (cea) above institutional upper limit of normal (range 0.0 - 5.2 ng/ml). * presence of measurable disease on imaging via recist v1.1. * ecog performance status 0-1. * participants must have adequate organ and marrow function as defined in the protocol. * a negative pregnancy test for pre-menopausal women of childbearing potential. * pre-menopausal women of childbearing potential who are sexually active with a male partner must agree to use adequate contraception prior to the study, for the duration of study participation. * inclusion of minorities: patients of all races and ethnic groups who meet the above inclusion and below exclusion criteria are eligible for this trial. * stated willingness to comply with all study procedures and availability for the duration of the study. * ability to understand and the willingness to sign a written informed consent document or have a legally authorized representative sign on the participant's behalf. exclusion criteria: * have previously received fulvestrant for treatment of their breast cancer. * history of allergic reactions attributed to the study drugs. * documented brain metastasis or active or newly diagnosed cns metastases, including meningeal carcinomatosis, because systemic treatment would need to be paused for these patients. * treatment with any investigational compound within 30 days prior to the first dose of study drugs or during this study. * diagnosis or treatment for another systemic malignancy within 2 years before the first dose of study drugs, or previously diagnosed with another malignancy and have any evidence of residual disease. patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. * uncontrolled intercurrent illness including-but not limited to-ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * patients with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis. * known history of testing positive for human immunodeficiency virus (hiv) or known acquired immunodeficiency syndrome. * active infection including tuberculosis, hepatitis b (known positive hbv surface antigen \[hbsag\]), or hepatitis c (hcv). participants with a past or resolved hbv infection (defined as the presence of hepatitis b core antibody \[anti-hbc\] and absence of hbsag) are eligible. participants with positive hcv antibody are eligible if polymerase chain reaction is negative for hcv rna. * concurrent or prior use of immunosuppressive medication within 14 days before the first dose of study drugs, with the following exceptions: premedication with dexamethasone, intranasal, inhaled, topical or local steroid injections, systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or its equivalent; steroids as premedication for hypersensitivity reactions (e.g., premedication for iodinated contrast allergy before ct scan). * inability to comply with protocol requirements. * pregnant and/or breastfeeding women are excluded.