gene signatures to guide hr+mbc therapy in a diverse cohort

Conditions: Invasive Mammary Carcinoma; Metastatic Breast Cancer

Summary: this is an open-label, multicenter, two-arm phase ii clinical trial that will evaluate the impact of 2nd line chemotherapy (i.e. capecitabine) on survival in patients with non-luminal a hormone receptor-positive (hr+) metastatic breast cancer (mbc)

primary objective: - determine the impact of early chemotherapy (i.e., capecitabine) versus endocrine therapy-based regimen on anti-tumor effect in patients with non-luminal a hormone receptor-positive (hr+) metastatic breast cancer secondary objectives: * compare the safety and tolerability of capecitabine versus endocrine therapy in patients with non-luminal a hormone receptor-positive (hr+) metastatic breast cancer * determine the impact of early chemotherapy (i.e., capecitabine) versus endocrine therapy-based regimen on anti-tumor effect in patients with non-luminal a hormone receptor-positive (hr+) metastatic breast cancer correlatives: * determine if the tumor mutations detected in cfdna are early surrogates of response * determine if the cfdna results at disease progression show new genomic alterations potentially associated with resistance to therapy

Eligibility criteria:
inclusion criteria: * signed and dated written informed consent. * subjects ≥ 18 years of age. * eastern cooperative oncology group (ecog) performance status 0 or 1. * clinical stage iv invasive mammary carcinoma or unresectable locoregional recurrence of invasive mammary carcinoma that is: * er (\>/=1%) and/or pr (\>/= 1%) by ihc and her2 negative (by ihc or fish) * previously exposed to an aromatase inhibitor (ai) or a selective estrogenreceptor modulator/ downregulator (serm; serd) + a cdk4/6 inhibitor. * prior radiation permitted (if completed at least 2 weeks prior to study entry. patients who have received prior radiotherapy must have recovered from toxicity (≤ grade 1) induced by this treatment (except for alopecia) * patients with brain metastasis secondary to breast cancer and clinically stable for more than 4 weeks from completion of radiation treatment and off steroids * evaluable disease (measurable or non-measurable) * measurable disease, ie, at least 1 measurable lesion as per recist 1.1 (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation) * patients with bone only disease allowed if possible to evaluate on radiological exams (eg.bone scan, pet/ct, ct, mri) even if lesions are non-measurable according to recist1.1. * adequate organ function including: * absolute neutrophil count (anc) ≥ 1.5 × 10\^9/l * platelets ≥ 100 × 10\^9/l * hemoglobin ≥ 8/g/dl (may have been transfused) * total serum bilirubin ≤ 1.5 times upper limit of normal (uln) * aspartate aminotransferase (ast/sgot) and alanine aminotransferase (alt/sgpt) ≤ 2.5 × uln (or ≤ 5 × uln if liver metastases are present) * serum creatinine ≤ 1.5 x uln or estimated creatinine clearance ≥ 50ml/min as calculated using the cockcroft-gault (cg) equation * for randomized patients only: tumors must be diagnosed as non-luminal a using the blueprint® and mammaprint® tests exclusion criteria: * prior chemotherapy in the metastatic setting * previous malignant disease other than breast cancer within the last 2 years with associated competing risk, with the exception of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or low-risk cancers considered curatively treated (i.e. complete remission achieved at least 2 years prior to first dose of study drugs and additional therapy not required while receiving study treatment). * persisting symptoms related to prior therapy that has not reduced to grade 1 \[national cancer institute common toxicity criteria for adverse events (nci ctcae) version 5.0\]; however, menopausal symptoms, alopecia, and sensory neuropathy grade ≤ 2 is acceptable * pregnant or breastfeeding females.