overcoming therapy resistance in er+ breast cancer patients: a translational project (overture)

Conditions: Breast Cancer

Summary: patients presenting with a de novo diagnosis of luminal-like advanced breast cancer (abc) or with disease recurrence after \>12 months from the end of adjuvant et, are generally candidate to a first line therapy with an aromatase inhibitor in association with a cdk4/6i. disease recurrence in \<12 months from the end of adjuvant et defines the disease as "endocrine resistant" and identifies patients that should receive a first line therapy with the selective estrogen receptor degrader (serd) fulvestrant in association with the cdk4/6i ribociclib, according to the results of the monaleesa-3 trial. a significant percentage of abc patients develops a primary resistance with disease progression within the first 6 months from the beginning of the treatment. furthermore, another relevant percentage of patients initially responding to the therapy, will later develop a secondary resistance, thus progressing after a median of 2 years from the beginning of the treatment. thereby, it is crucial to identify biomarkers that could be predictive of a response or a resistance to et and/or cdk4/6i, to provide the best therapeutic strategy, tailored upon both clinico-pathological and molecular characteristics. numerous pathways associated with resistance to cdk4/6i have been investigated by means of liquid biopsy analysis. the aim of this study is to identify potential biomarkers predictive of a clinical benefit in patients receiving a first line therapy with ai/fulvestrant (+/- lh-rh analogue) in association with a cdk4/6i for luminal-like advanced breast cancer.

patients presenting with a de novo diagnosis of luminal-like advanced breast cancer (abc) or with disease recurrence after \>12 months from the end of adjuvant et, are generally candidate to a first line therapy with an aromatase inhibitor (+/- lh-rh analogue depending from the menopausal status) in association with a cdk4/6i. disease recurrence in \<12 months from the end of adjuvant et defines the disease as "endocrine resistant" and identifies patients that should receive a first line therapy with the selective estrogen receptor degrader (serd) fulvestrant in association with the cdk4/6i ribociclib, according to the results of the monaleesa-3 trial. the choice of the endocrine backbone and of the cdk4/6i is mostly influenced by the patient's clinical characteristics and by disease factors. however, a significant percentage of abc patients develops a primary resistance with disease progression within the first 6 months from the beginning of the treatment. furthermore, another relevant percentage of patients initially responding to the therapy, will later develop a secondary resistance, thus progressing after a median of 2 years from the beginning of the treatment. thereby, it is crucial to identify biomarkers that could be predictive of a response or a resistance to et and/or cdk4/6i, to provide the best therapeutic strategy, tailored upon both clinico-pathological and molecular characteristics. numerous pathways associated with resistance to cdk4/6i have been investigated by means of liquid biopsy analysis. the aim of this study is to identify potential biomarkers predictive of a clinical benefit in patients receiving a first line therapy with ai/fulvestrant (+/- lh-rh analogue) in association with a cdk4/6i for luminal-like advanced breast cancer.

Eligibility criteria:
inclusion criteria: * histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease. * er positive tumor ≥ 1% * her2 negative breast cancer by fish or ihc (ihc 0,1+, 2+ and/or fish her2: cep17 ratio \< 2.0) * females, 18 years of age or older * candidate to first-line endocrine therapy (lh-rh analogue for pre-menopausal women is allowed) * signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. * willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. exclusion criteria: * diagnosis of any secondary malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix. * prior endocrine therapy for metastatic disease * prior chemotherapy for metastatic disease * patients unwilling to or unable to comply with the protocol. * known cns metastases