Pharmacogenomic Study of Neoadjuvant Eribulin for HER2 Non-overexpressing Breast Cancer

This is a prospective, non-randomized, open-label, multicenter, single-arm exploratory pharmacogenomic study of single agent eribulin as neoadjuvant therapy in patients with operable Stage III HER2 non-overexpressing breast cancer.


Eligibility Criteria:
Inclusion Criteria:

* Written informed consent, specifically highlighting the molecular characterization of tumor and genomic samples
* Age ≥18 years
* Histologically confirmed invasive breast carcinoma, with all of the following characteristics:

  * Primary tumor ≥2cm in largest diameter (cT1-3)
  * cN0-1
  * No evidence of distant metastasis (M0)
* Breast cancer (BC) eligible for primary surgery
* Available pre-treatment core (Tru-cut) biopsy or possibility of performing one
* HER2-negative BC (as per local assessment), defined as either of the following:

  * 0-1+ expression by IHC
  * 2+ expression by IHC and in situ hybridization (FISH/CISH) without HER2 gene amplification (\<4 HER2 gene copies per nucleus, or a FISH ratio \[HER2 gene copies to Cr17 signals\] of \<1.8)
  * Is situ hybridization (FISH/CISH) without HER2 gene amplification, independently of IHC
* Known hormone receptor (ER/PgR) status (as per local assessment) or the possibility of performing the tests
* Known percentage of hormone receptor (ER/PgR) and Ki67-positive tumor cells (as per local assessment), or possibility of performing the tests
* In the case of a multifocal tumor, the largest lesion must be ≥2 cm and designated the "target" lesion for all subsequent tumor evaluations and HER2-negative status must be documented in all the tumor foci
* ECOG performance status of 0 or 1
* Laboratory values as follows:

  * Absolute neutrophil count (ANC) ≥1.5 x 109/L
  * Platelets count ≥100 x 109/L
  * Hemoglobin ≥9 g/dL
  * Serum bilirubin ≤1.5 time the upper limit of normal (ULN)
  * Alanine aminotransferase and aspartate aminotransferase (AST) ≤2.5 x ULN
  * Alkaline phosphatase ≤2.5 x ULN
  * Serum creatinine ≤1.5 mg/dL or calculated creatinine clearance ≥60 mL/m
* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol
* Availability of genomic DNA (via whole blood)

Exclusion Criteria:

* Any prior treatment for primary invasive BC
* Metastatic, locally advanced or inflammatory (i.e., Stage III-IV) BC
* Bilateral invasive BC
* Multicentric BC, defined as the presence of two or more foci of cancer in different quadrants of the same breast
* Pre-existing peripheral neuropathy of any grade
* Uncontrolled hypertension (systolic \>150 mmHg and/or diastolic \>100 mmHg)
* Clinically significant (i.e., active) cardiovascular disease
* Long QT syndrome
* Concomitant use of inhibitors of hepatic transport proteins such as organic anion-transporting proteins, P-glycoprotein, multidrug resistant proteins etc
* Major medical conditions that might affect study participation (e.g., uncontrolled seizure disorder, uncontrolled pulmonary, renal or hepatic dysfunction, or uncontrolled infection)
* Other primary malignant tumors within the previous 5 years, except for adequately controlled limited basal cell carcinoma of the skin or carcinoma in situ of the cervix
* Known human immunodeficiency virus(HIV) infection or other active or serious infection requiring IV antibiotics at randomization
* Pregnancy or breastfeeding women
* Women of childbearing potential(\<2 years after the last menstruation) not using effective, non-hormonal means of contraception during the study and for a period of 6 months following the last administration of study drug
* Administration of any live virus vaccine within 8 weeks preceding study entry
* Use of any investigational agent within 30 days of administration of the first dose of study drug or concurrent treatment on another clinical study
* Requirement for radiation therapy concurrent with study anticancer treatment
* Known hypersensitivity to any of the study drugs or excipients
* Inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee