Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER).

BACKGROUND: The potential benefit of adding palbociclib to fulvestrant as first-line treatment in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative endocrine-sensitive advanced breast cancer (ABC) patients remains uncharacterized. PATIENTS AND METHODS: In this randomized (1:1), double-blind, phase II study, postmenopausal women with HR-positive, HER2-negative ABC with de novo metastatic disease or those who relapsed after >12 months of adjuvant endocrine therapy received palbociclib/fulvestrant or placebo/fulvestrant. Stratification was based on recurrent versus de novo metastatic disease and visceral involvement. The primary objective was one-year progression-free survival (PFS-1y) rate. The sample size was 190 patients. The two-sided alpha of 0.2, 80% of power to detect a difference between the arms, assuming PFS rates of 0.695 and 0.545 for palbociclib/fulvestrant and placebo/fulvestrant, respectively. RESULTS: In total, 189 patients were randomized to palbociclib/fulvestrant ([n = 94] or placebo/fulvestrant [n = 95]). 45.5% and 60.3% of patients had de novo metastatic disease and visceral involvement, respectively. PFS-1y rates were 83.5% and 71.9% in the palbociclib/fulvestrant and placebo/fulvestrant arms, (HR 0.55, 80% CI 0.36-0.83, P = 0.064). The median PFS were 31.8 and 22.0 months for the palbociclib/fulvestrant and placebo/fulvestrant arms (aHR 0.48, 80% CI 0.37-0.64, P = 0.001). The most frequent grade 3-4 adverse events were neutropenia (68.1% vs. 0%), leucopenia (26.6% vs. 0%), anemia (3.2% vs. 0%), and lymphopenia (14.9% vs. 2.1%) for the palbociclib/fulvestrant and placebo/fulvestrant, respectively. The most frequent non-hematologic grade 3-4 adverse event was fatigue (4.3% vs. 0%). CONCLUSIONS: Palbociclib/fulvestrant demonstrated better PFS-1y rates and median PFS than placebo/fulvestrant in HR-positive/HER2-negative endocrine-sensitive ABC patients.

Biomarkers in breast cancer: a consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology

This consensus statement revises and updates the recommendations for biomarkers use in the diagnosis and treatment of breast cancer, and is a joint initiative of the Spanish Society of Medical Oncology and the Spanish Society of Pathology. This expert group recommends determining in all cases of breast cancer the histologic grade and the alpha-estrogen receptor (ER), progesterone receptor, Ki-67 and HER2 status, in order to assist prognosis and establish therapeutic options, including hormone therapy, chemotherapy and anti-HER2 therapy. One of the four available genetic prognostic platforms (MammaPrint®, Oncotype DX®, Prosigna® or EndoPredict®) may be used in node-negative ER-positive patients to establish a prognostic category and decide with the patient whether adjuvant treatment may be limited to hormonal therapy. Newer technologies including next-generation sequencing, liquid biopsy, tumour-infiltrating lymphocytes or PD-1 determination are at this point investigational

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Correction to: Biomarkers in breast cancer: A consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

On page 5 of the article, in the last paragraph of the section "Prognostic genetic platforms: molecular phenotypes and translation to the clinic" a relevant discrepancy between the text and Table 1 could be misunderstood, therefore the paragraph was corrected.

Assessment of neuronal autoantibodies in patients with small cell lung cancer treated with chemotherapy with or without ipilimumab.

Small-cell lung cancer (SCLC) is often associated with paraneoplastic syndromes. To assess the role of anti-neuronal autoantibodies (NAAs) as biomarkers of treatment outcome, we assessed NAAs in serial samples from SCLC patients treated with chemoimmunotherapy compared to chemotherapy alone. We evaluated 2 cohorts: in cohort 1 (C1), 47 patients received standard platinum/etoposide, and in cohort 2 (C2), 38 patients received ipilimumab, carboplatin and etoposide. Serum samples at baseline and subsequent time points were analyzed for the presence of NAAs. NAAs were detected at baseline in 25 patients (53.2%) in C1 and in 20 patients (52.6%) in C2 (most frequently anti-Sox1). NAA at baseline was associated with limited disease (75% vs 50%; p: 0.096) and better overall survival (15.1 m vs 11.7 m; p: 0.032) in C1. Thirteen patients (28.9%) showed 2 or more reactivities before treatment; this was associated with worse PFS (5.5 m vs 7.3 m; p: 0.005) in patients treated with chemoimmunotherapy. NAA titers decreased after therapy in 68.9% patients, with no differential patterns of change between cohorts. Patients whose NAA titer decreased after treatment, showed longer OS [18.5 m (95% CI: 15.8 - 21.2)] compared with those whose NAA increased [12.3 m (95% CI: 8.1 - 16.5; p 0.049)], suggesting that antibody levels correlate to tumor load. Our findings reinforce the role of NAAs as prognostic markers and tumor activity/burden in SCLC, warrant further investigation in their predictive role for immunotherapy and raise concern over the use of immunotherapy in patients with more than one anti-NAA reactivity.

Biomarkers in breast cancer: A consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

This consensus statement revises and updates the recommendations for biomarkers use in the diagnosis and treatment of breast cancer, and is a joint initiative of the Spanish Society of Medical Oncology and the Spanish Society of Pathology. This expert group recommends determining in all cases of breast cancer the histologic grade and the alpha-estrogen receptor (ER), progesterone receptor, Ki-67 and HER2 status, in order to assist prognosis and establish therapeutic options, including hormone therapy, chemotherapy and anti-HER2 therapy. One of the four available genetic prognostic platforms (MammaPrint®, Oncotype DX®, Prosigna® or EndoPredict®) may be used in node-negative ER-positive patients to establish a prognostic category and decide with the patient whether adjuvant treatment may be limited to hormonal therapy. Newer technologies including next-generation sequencing, liquid biopsy, tumour-infiltrating lymphocytes or PD-1 determination are at this point investigational.

A definition for aggressive disease in patients with HER-2 negative metastatic breast cancer: an expert consensus of the Spanish Society of Medical Oncology (SEOM)

Purpose. To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology. Methods. A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement. Results. Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12-24 months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival. Conclusions. High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches (AU)

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Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients.

BACKGROUND: RAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice. PATIENTS AND METHODS: RAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated. RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients. RESULTS: Analysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment. CONCLUSION: The high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments.

A definition for aggressive disease in patients with HER-2 negative metastatic breast cancer: an expert consensus of the Spanish Society of Medical Oncology (SEOM).

PURPOSE: To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology. METHODS: A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement. RESULTS: Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12-24 months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival. CONCLUSIONS: High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches.

Trastuzumab emtansine (T-DM1) plus docetaxel with or without pertuzumab in patients with HER2-positive locally advanced or metastatic breast cancer: results from a phase Ib/IIa study.

BACKGROUND: Trastuzumab emtansine (T-DM1) exhibited enhanced antitumor activity when combined with docetaxel or pertuzumab in preclinical studies. This phase Ib/IIa study assessed the feasibility of T-DM1 + docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and T-DM1 + docetaxel ± pertuzumab in patients with HER2-positive locally advanced breast cancer (LABC). PATIENTS AND METHODS: Phase Ib (part 1) explored dose escalation, with T-DM1 + docetaxel administered for greater than or equal to six cycles in patients with MBC. Phase Ib (part 2) began with the maximum tolerated dose (MTD) identified in part 1. Patients with LABC were administered less than or equal to six cycles of T-DM1 + docetaxel or T-DM1 + docetaxel + pertuzumab. Phase IIa explored the MTDs identified in phase Ib. RESULTS: Administered with T-DM1 (3.6 mg/kg), the docetaxel MTD was 60 mg/m(2) in MBC. In LABC, the MTD was 100 mg/m(2) docetaxel in combination with T-DM1 (3.6 mg/kg), given with granulocyte colony-stimulating factor (G-CSF). Administered with T-DM1 (3.6 mg/kg) + pertuzumab (840 mg, cycle 1; 420 mg, subsequent cycles), the docetaxel MTD in LABC was 75 mg/m(2) with G-CSF support. Neutropenia was the most common grade 3-4 adverse event (AE; MBC, 72% and LABC, 29%). In total, 48% (12/25) of MBC patients and 47% (34/73) of LABC patients experienced AEs requiring dose modification. In MBC (median prior systemic agents = 5), the objective response rate was 80.0% (20/25; 95% confidence interval [CI] 59.3-93.2) and the median progression-free survival was 13.8 months (range, 1.6-33.5). The pathologic complete response (ypT0/is, ypN0) rate in LABC was 60.3% (44/73; 95% CI 48.1-71.5). Pharmacokinetic analyses indicated a low risk of drug-drug interaction between T-DM1 and docetaxel. CONCLUSIONS: T-DM1 combined with docetaxel ± pertuzumab appeared efficacious in MBC or LABC; however, nearly half of patients experienced AEs requiring dose reductions with these T-DM1 combinations. CLINICALTRIALSGOV IDENTIFIER: NCT00934856.

Evolución de la DMO durante el tratamiento con inhibidores de aromatasa y su relación con el gen CYP11A1: estudio prospectivo de la cohorte B-ABLE / BMD evolution during treatment with aromatase inhibitors and its relation to the CYP11A1 gene: prospective study in the B-ABLE cohort

Objetivos: El objetivo del estudio fue analizar los cambios en la densidad mineral ósea (DMO) a lo largo del tratamiento con inhibidores de aromatasa (IA) en la práctica clínica y evaluar la asociación entre el gen CYP11A1 y la variación de DMO al final del tratamiento. Material y métodos: La cohorte B-ABLE es un estudio prospectivo de mujeres postmenopáusicas con cáncer de mama, en tratamiento con IA. Se analizó la variación de DMO durante todo el tratamiento con IA, así como las diferencias entre las pacientes tratadas y no-tratadas previamente con tamoxifeno (TMX). Tres polimorfismos (rs4077581, rs11632698 y rs900798) del gen CYP11A1, fueron genotipados para su asociación con la variación de DMO. Resultados: Las pacientes tratadas con TMX mostraron pérdidas más aceleradas de DMO que las no tratadas previamente con TMX (60% menos en columna y 46% en fémur a los 2 años y 70% menos en columna y 63% en fémur a los 3 años). No obstante, al final del tratamiento no se detectaron diferencias significativas en la pérdida de DMO entre ambos grupos de pacientes. Los 3 polimorfismos del gen CYP11A1 resultaron significativamente asociados a la variación de DMO en fémur al final del tratamiento. Conclusiones: La DMO disminuyó de forma más acelerada en las pacientes con tratamiento previo con TMX que en las que solo recibieron AI, a pesar de que no se detectaron diferencias significativas al final de tratamiento. Polimorfismos en el gen CYP11A1 están relacionados con la variación de la DMO en respuesta al tratamiento con IA (AU)

Objectives: The aim of this study was to analyze bone mineral density (BMD) changes throughout aromatase inhibitor (AI) treatment in clinical cases and also consider its association with the CYP11A1 gene and the BMD variation after treatment. Material and methods: The B-ABLE cohort is a prospective study of postmenopausal women with breast cancer, in AI treatment. BMD variation was analyzed during AI treatment, as well as the differences those patients who were treated and not treated previously with tamoxifen (TMX). Three polymorphisms (rs4077581, rs11632698 and rs900798) of the CYP11A1 gene were genotyped for their association with BMD variation. Results: TMX-treated patients presented more rapid BMD loss than those who did not undergo prior TMX treatment (60% less in spine and 46% in femur at 2 years and 70% less in the spine and 63% in the femur at 3 years). However, no significant BMD loss was detected after treatment in either group. The 3 CYP11A1 gene polymorphisms were significantly associated with BMD variation in the femur at the end of the treatment. Conclusions: BMD was reduced more rapidly in patients with prior TMX treatment than in those who only received AI, although no significant differences were detected after treatment. The 3 CYP11A1 gene polymorphisms were associated with BMD variation in response to AI treatment (AU)

Subcutaneous trastuzumab: drug development and current position

HER2-positive breast cancer, accounting for 15 % of the total breast cancer patient population, carries in itself a bad prognosis, which has now become much better after the advent of anti-HER2 drugs. HER2-targeted therapy has significantly improved disease free- and overall survival in HER2-positive breast cancer, and has rendered better disease control both in the early and advanced disease setting. Trastuzumab treatment duration is often prolonged and poses significant time and resource challenges both on the treatment institutions and on the patient. The recent development of a subcutaneous formulation has meant a significant advance in this respect. We review the drug development of the compound and the current evidence on its use (AU)

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Predicting response and survival in chemotherapy-treated triple-negative breast cancer.

BACKGROUND: In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). METHODS: Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. RESULTS: Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. CONCLUSIONS: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.

Subcutaneous trastuzumab: drug development and current position.

HER2-positive breast cancer, accounting for 15 % of the total breast cancer patient population, carries in itself a bad prognosis, which has now become much better after the advent of anti-HER2 drugs. HER2-targeted therapy has significantly improved disease free- and overall survival in HER2-positive breast cancer, and has rendered better disease control both in the early and advanced disease setting. Trastuzumab treatment duration is often prolonged and poses significant time and resource challenges both on the treatment institutions and on the patient. The recent development of a subcutaneous formulation has meant a significant advance in this respect. We review the drug development of the compound and the current evidence on its use.

Trastuzumab or lapatinib with standard chemotherapy for HER2-positive breast cancer: results from the GEICAM/2006-14 trial.

BACKGROUND: The addition of trastuzumab (T) and lapatinib (L) to neoadjuvant chemotherapy increases the pathological complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We investigated the efficacy of T or L with neoadjuvant chemotherapy and specific efficacy biomarkers. METHODS: Patients with stages I-III (including inflammatory) HER2-positive breast cancer were randomised to receive epirubicin (E) plus cyclophosphamide (C) × 4 cycles followed by docetaxel (D) plus either T (EC-DT) or L (EC-DL). End points included pCR (primary), clinical response, toxicity, and pCR-predictive biomarkers. RESULTS: We randomised 102 patients to EC-DT (50) and EC-DL (52). Median age was 48, 56% were premenopausal and 58% had oestrogen receptor (ER)-positive tumours. Pathological complete response in breast was 52.1% (95% CI:38.0-66.2%) for EC-DT and 25.5% (95% CI:13.5-37.5%) for EC-DL (P=0.0065). Pathological complete response in breast and axilla was 47.9% for EC-DT and 23.5% for EC-DL (P=0.011). Grade 3-4 toxicity did not differ across treatments, except for diarrhoea (2% in EC-DT vs 13.5% in EC-DL, P=0.030). Multivariate analyses showed that treatment (P=0.036) and ER (P=0.014) were the only predictors of pCR in both groups. CONCLUSION: EC-DT exhibited higher efficacy and lower toxicity than EC-DL. Of the different biomarkers studied, only the absence of ER expression was associated with increased pCR.

Pilot study on workload estimate in breast cancer, lung cancer and colorectal cancer in a Medical Oncology Service at Valme hospital

New advances in the diagnosis and treatment of cancer and the increased incidence and prevalence of this disease have led to an increase in the number and duration of visits in Medical Oncology in the last few years. Based on the functions of a medical oncologist and the time recommended for each work activity established by the Spanish Society of Medical Oncology (SEOM), we carried out a pilot study on the three most frequent neoplasias in our country [breast cancer (BC), lung cancer (LC) and colorectal cancer (CRC)], in order to determine the real time each patient requires from a physician and thus establish a recommendation on the number of medical oncologists necessary. Using the actual itinerary of the first 20 patients of 2009 in each of the three neoplasias seen at the Medical Oncology Service of the Virgen de Valme University Hospital, we measured the number of visits, the antineoplastic treatments received, the number of hospital admissions and average length of stay. During the years following the study, these data were estimated based on the natural history of each neoplasia. During the first year, the average time spent by the medical oncologist was 235, 390 and 265 min on each outpatient with BC, LC and CRC, respectively. In hospitalisation, the average oncologist/patient minutes were 40, 360 and 118 for BC, LC and CRC, respectively. Finally, the time spent on each visit or day of hospitalisation was that recommended by the SEOM, achieving an ultimate ratio of 1 oncologist for every 83 first visits (AU)

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.

Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) for 4 cycles) followed either by D (docetaxel 100 mg/m(2) × 4 cycles; EC-D) or DCb (docetaxel 75 mg/m(2) plus carboplatin AUC 6 × 4 cycles; EC-DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC-D, 48 EC-DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC-D and 14 patients (30 %) with EC-DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56-83) in the EC-D arm and 77 % (95 % CI 65-87) in the EC-DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC-D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.

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.

BACKGROUND: Luminal breast cancer is a highly endocrine responsive disease. However, the therapeutic benefit of chemotherapy (CT) in this population is not fully characterized. This study investigates the value of CT and hormone therapy (HT) in luminal breast cancer patients in the neoadjuvant setting. PATIENTS AND METHODS: Patients with operable breast cancer and immunophenotypically defined luminal disease (ER+/PR+/HER2-/cytokeratin 8/18+) were recruited. Patients were randomized to CT (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) 4 cycles followed by docetaxel 100 mg/m(2 )4 cycles [EC-T]) or HT (exemestane 25 mg daily 24 weeks [combined with goserelin in premenopausal patients]). The primary end point was the clinical response measured by magnetic resonance imaging. RESULTS: Ninety-five patients were randomized (47 CT, 48 HT). The clinical response rate was 66% for CT and 48% for HT (P = 0.075). We performed an unplanned analysis based on Ki67 levels (cut-off of 10%). Similar clinical response was seen between arms in patients with low Ki67 (CT: 63%, HT: 58%; P = 0.74); patients with high Ki67 had a better response with CT (67 versus 42%; P = 0.075). Grade 3/4 toxicity was more frequent with CT. CONCLUSIONS: Luminal immunophenotype is not enough to identify patients who do not benefit from neoadjuvant CT. Luminal patients with low proliferation index could potentially avoid CT.