Selective Neoadjuvant Treatment According to Immunohistochemical Subtype for HER2 Negative Breast Cancer Patients

This is an open-label study that includes two substudies of random distribution. First,a sample of the primary tumor will be obtained and will be analyzed by an immunohistochemical technique to determine several markers.Depending on the expression of these markers, the patients will be characterize as group 1 (Luminal A phenotype) or group 2 (Basal phenotype) and a random assignment will be performed to standard or experimental treatment.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

* Written informed consent.
* Breast cancer with histological diagnosis.
* Negative Human Epidermal Growth Factor Receptor 2 (HER2) tumours defined as immunohistochemistry (IHQ) 0,1+.
* No evidence of suspicion of metastatic disease.
* Age \>= 18 years old.
* Performance status (Karnofsky index) \>= 80 (ECOG 0,1).
* Adequate cardiac function by ECG in the previous 12 weeks.
* Hematology: neutrophils \>= 1,5 x10\^9/l; platelets \>= 100 x10\^9/l; hemoglobin \>= 10 g/dl.
* Adequate hepatic function: total bilirubin \<= 1x Upper Normal Limit (UNL); Aspartate aminotransferase (AST) (SGOT) and Alanine aminotransferase (ALT) (SGPT) \<= 2.5 x UNL; alkaline phosphatase \<= 2.5 x UNL.
* Adequate renal function: creatinine \<= 1 x UNL; creatinine clearance \>= 60 ml/min.
* Patients able to comply with study treatment and follow-up.
* Negative pregnancy test in the previous 14 days.

Exclusion Criteria:

* HER2 positive tumours (defined as IHQ 3+ or positive fluorescence in situ hybridization \[FISH\]).
* Prior systemic therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
* Prior treatment with anthracyclines or taxanes (paclitaxel, docetaxel) for any previous malignancy.
* Prior radiotherapy for breast cancer.
* Bilateral invasive breast cancer.
* Pregnant or lactating women.
* Previous grade \>= 2 motor or sensorial neurotoxicity (National Cancer Institute Common Toxicity Criteria \[NCICTC\]).
* Other serious comorbidities: congestive heart failure or unstable angina; prior history of myocardial infarction in previous year; uncontrolled hypertension (HT); high risk arrhythmias; history of significant neurological or psychiatric disorders; uncontrolled active infection; active peptic ulcer; unstable diabetes mellitus; dyspnea at rest; or chronic therapy with oxygen.
* Previous or current history of neoplasms different from breast cancer, except for skin carcinoma, cervical in situ carcinoma, or any other tumor curatively treated and without recurrence in the last 10 years; ductal in situ carcinoma in the same breast; lobular in situ carcinoma.
* Chronic treatment with corticosteroids.
* Contraindications for administration of corticosteroids.
* Concomitant treatment with other therapy for cancer.
* Males.

• RESULTAlba E, Chacon JI, Lluch A, Anton A, Estevez L, Cirauqui B, Carrasco E, Calvo L, Segui MA, Ribelles N, Alvarez R, Sanchez-Munoz A, Sanchez R, Garcia-Asenjo JA, Rodriguez-Martin C, Escudero MJ, Albanell J. A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study. Breast Cancer Res Treat. 2012 Nov;136(2):487-93. doi: 10.1007/s10549-012-2100-y. Epub 2012 Oct 9. PMID 23053638
• RESULTAlba E, Calvo L, Albanell J, De la Haba JR, Arcusa Lanza A, Chacon JI, Sanchez-Rovira P, Plazaola A, Lopez Garcia-Asenjo JA, Bermejo B, Carrasco E, Lluch A; GEICAM. Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study. Ann Oncol. 2012 Dec;23(12):3069-3074. doi: 10.1093/annonc/mds132. Epub 2012 Jun 6. PMID 22674146
• RESULTPrat A, Lluch A, Albanell J, Barry WT, Fan C, Chacon JI, Parker JS, Calvo L, Plazaola A, Arcusa A, Segui-Palmer MA, Burgues O, Ribelles N, Rodriguez-Lescure A, Guerrero A, Ruiz-Borrego M, Munarriz B, Lopez JA, Adamo B, Cheang MC, Li Y, Hu Z, Gulley ML, Vidal MJ, Pitcher BN, Liu MC, Citron ML, Ellis MJ, Mardis E, Vickery T, Hudis CA, Winer EP, Carey LA, Caballero R, Carrasco E, Martin M, Perou CM, Alba E. Predicting response and survival in chemotherapy-treated triple-negative breast cancer. Br J Cancer. 2014 Oct 14;111(8):1532-41. doi: 10.1038/bjc.2014.444. Epub 2014 Aug 7. PMID 25101563
• RESULTPrat A, Lluch A, Turnbull AK, Dunbier AK, Calvo L, Albanell J, de la Haba-Rodriguez J, Arcusa A, Chacon JI, Sanchez-Rovira P, Plazaola A, Munoz M, Pare L, Parker JS, Ribelles N, Jimenez B, Bin Aiderus AA, Caballero R, Adamo B, Dowsett M, Carrasco E, Martin M, Dixon JM, Perou CM, Alba E. A PAM50-Based Chemoendocrine Score for Hormone Receptor-Positive Breast Cancer with an Intermediate Risk of Relapse. Clin Cancer Res. 2017 Jun 15;23(12):3035-3044. doi: 10.1158/1078-0432.CCR-16-2092. Epub 2016 Nov 30. PMID 27903675
• RESULTAlba E, Lluch A, Ribelles N, Anton-Torres A, Sanchez-Rovira P, Albanell J, Calvo L, Garcia-Asenjo JA, Palacios J, Chacon JI, Ruiz A, De la Haba-Rodriguez J, Segui-Palmer MA, Cirauqui B, Margeli M, Plazaola A, Barnadas A, Casas M, Caballero R, Carrasco E, Rojo F. High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer. Oncologist. 2016 Feb;21(2):150-5. doi: 10.1634/theoncologist.2015-0312. Epub 2016 Jan 19.