Eliminate: This phase II trial is evaluating the effectiveness of standard neoadjuvant chemotherapy alone and in combination with an aromatase inhibitor (a drug used in post menopausal women) in the treatment of oestrogen receptor positive breast cancerRandomised phase II trial of neoadjuvant chemotherapy +/- concurrent aromatase inhibitor endocrine therapy to down-stage large oestrogen receptor positive breast cancer

Inclusion

* Female >= 18 years.
* Intact histologically confirmed grade 2 or 3 invasive breast cancer on core biopsy.
* ER positive (>= 10% cells) on core biopsy.
* HER2 negative (IHC 0 or 1+ or ISH negative breast cancer on core biopsy). Negative ISH test is required if HER2 testing shows IHC 2+.
* The primary breast tumour measures > 20 mm by ultrasound and/or mammogram (clinical stage cT2-4). In the case of a multifical tumour (defined as the presence of two or more foci of cancer within the same breast quadrant), the largest lesion must be >20 mm.
* Clinical stage II or stage III disease as defined by Protocol Appendix D.
* Clinically and pathologically suitable for neoadjuvant chemotherapy of at least 18 weeks duration (i.e. minimum of 6 three-weekly cycles) that includes an anthracycline and a taxane.
* Willing to undergo breast core biopsies for research purposes on 2 occasions prior to surgery.
* Surgeon has a realistic expectation that either mastectomy or breast conservation surgery will be feasible at the end of neoadjuvant treatment to achieve a complete surgical resection.
* Patient and surgeon agree to axillary node dissection if clinical or radiologic examination after neoadjuvant therapy suggests lymph node involvement
* Patient and surgeon agree in cases of cytologically positive (FNA/core) axilla at diagnosis, that converts after neoadjuvant therapy to a negative axilla on clinical examination and imaging, that an axillary dissection will be performed unless 3 sentinel nodes can be removed using dual mapping technique.
* Any menopausal status. A serum or urine test must be carried out on all women of child-bearing potential (pre- or perimenopausal status) to exclude pregnancy. Patients must cease all hormonal contraception and hormone replacement therapies from the time of informed consent. Patients of child-bearing potential must agree to use at least one form of adequate non-hormonal contraception (e.g. barrier method of birth control; abstinence) from the time of signing informed consent.
- Patients will be clinically defined as pre- or perimenopausal unless one of the following criteria is met for the definition of postmenopausal: Patient with intact uterus and ovaries and age > 55 years and amenorrhea for > 1 year; Surgical bilateral oophorectomy; Postmenopausal oestradiol/LH/FSH levels.
* Patient has adequate bone marrow function:
- Neutrophil count > 1.5 x 10^9/L
- Platelets >= 100 x 10^9/L
- Haemoglobin > 100 g/L.
* Patient has adequate hepatic function:
- Bilirubin < upper limit of normal (ULN) for institution (except Gilbert’s disease)
- ALT/AST <= 2 x ULN for institution
- Alkaline phosphatase <= 2.5 x ULN for institution.
* Patient has adequate renal function:
- Creatinine within normal institutional limits OR
- eGFR > 60mL/min/1.73m^2
* Patient is able to provide signed informed consent, including consent for collection and storage of serial biological specimens