The ORR was reported including a 95% confidence interval. The estimate of the ORR was determined according to RECIST 1.1 and measured by MRI and mammogram in patients treated with this regimen. ORR was calculated as follows:

Overall Response Rate = Number of Complete Responses (CRs), Partial Responses (PRs) / ITT population

The ORR was reported including a 95% confidence interval. The estimate of the ORR was determined according to RECIST 1.1 and measured by MRI and mammogram in patients treated with this regimen. ORR was calculated as follows:

Overall Response Rate = Number of CRs, PRs / ITT population

IDFS was defined as the time (days) from the date of randomization until the date of objective recurrent disease (local, regional or distant), second primary invasive malignancy (breast or non-breast) or death from any cause. For patients not known to have died as of the data cut-off date and who do not have recurrent disease or second primary tumor, invasive disease-free survival will be censored at the last contact date. Ductal carcinoma in-situ (DCIS) will not be considered an event for the purpose of this analysis.

The conversion from the initially planned mastectomy to BCS was reported including a 95% confidence interval. The estimate of the rate of conversion to BCS was calculated as follows:

BCS rate = Number of patients with BCS / Number of patients with initially planned mastectomy.

Incidence of adverse events by maximum CTCAE grade (v4.03; NCI 2010) that occur during the study treatment period or within 30 days of the last dose of study treatment, regardless of causality and according to the relationship to study drug as assessed by the investigator, were collected and evaluated.

Ki67 was analysed by immunohistochemistry following the American Society of Clinical Oncology and the College of American Pathologists guidelines. The cut-off considered for Ki67 expression was 20% of positively stained tumor cells.

Caveolin (Cav)-1 was evaluated in the stroma and its expression was categorized in low, moderate, or high (tertile). The high expression of Cav-1 was considered as positive.

SPARC was evaluated for both tumor and stroma. Its expression was categorized as negative when the intensity was absent-to-weak (1), or moderate (11)-to-strong (111) with a proportion of stained cells <10%. Immunolabeling was positive if the intensity was moderate (11)-to-strong (111) and the extent of staining was 10%.

Molecular subtypes were classified according to St. Gallen criteria 2013 and Prat et al. into Luminal A (ER+, Progesterone Receptor (PgR) >20%, Human Epidermal growth factor Receptor 2 - (HER2), Ki67 <14%), Luminal B1 (ER+, HER2-, PgR >20% and/or Ki67 <14%), Luminal B2 (ER+, HER2+, any PgR, any Ki67), TN (ER-, PgR-, HER2-), and HER2-enriched (ER-, PgR-, HER2+) subtypes.

ECOG score runs from 0 to 5, with 0 denoting perfect health and 5 death. ECOG 0: Asymptomatic ECOG 1: Symptomatic but completely ambulatory ECOG 2: Symptomatic, <50% in bed during the day ECOG 3: Symptomatic, >50% in bed, but not bedbound ECOG 4: Bedbound ECOG 5: Death

Tumor (T) size describes the size of the tumour. Larger T is associated with inferior survival.

TX: can't be assessed. Tis: ductal carcinoma in situ. T1: tumour is 2 centimetres (cm) across or less. T1mi: tumour is 0.1cm across or less T1a: tumour >0.1 cm but <0.5 cm T1b: tumour >0.5 cm but <1 cm T1c: tumour >1 cm but <2 cm T2: tumour >2 cm but <5 cm across T3: tumour >5 cm across T4a: tumour has spread into the chest wall T4b: tumour has spread into the skin and the breast might be swollen T4c: tumour has spread to both the skin and the chest wall T4d: inflammatory carcinoma

Node (N) describes whether the cancer has spread to the Lymph Nodes (LN). Prognosis is better when cancer has not spread to the LN. The more LN that contain cancer, the poorer prognosis tends to be.

NX: LN can't be assessed N0: no Cancer Cells (CC) N1: CC in the LN in the armpit but the nodes are not stuck to surrounding tissues.

N2a: CC in the LN in the armpit, which are stuck to each other and to other structures.

N2b: CC in the LN behind the breast bone. N3a: CC in LN below the collarbone. N3b: CC in LN in the armpit and behind the breastbone.

Clinical Stages:

Stage 0: Abnormal cells are present but have not spread to nearby tissue. Also called carcinoma in situ (CIS). CIS is not cancer, but it may become cancer.

Stage I, Stage II, and Stage III: Cancer is present. The higher the number, the larger the cancer tumor and the more it has spread into nearby tissues.

Stage IV: The cancer has spread to distant parts of the body.

Cancer cells are given a Grade (G) when they are removed from the breast and checked under a microscope. The G is based on how much the cancer cells look like normal cells.

G1 or well differentiated (score 3, 4, or 5): cells are slower-growing, and look more like normal breast tissue.

G2 or moderately differentiated (score 6, 7): cells are growing at a speed of and look like cells somewhere between G1 and 3.

G3 or poorly differentiated (score 8, 9): cells look very different from normal and will probably grow and spread faster.

Objective Response was measured following the Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. For the purpose of this study a response is defined as the achievement of a complete or partial response measured by breast MRI.

Pathological complete response (pCR) was evaluated following the Symmans method at the time of the definitive surgery. For the purpose of this study RCB-0 was considered a pCR.

The pCR (RCB-0) rate (pCRR) was reported including a 95% confidence interval. The estimate of the pCR rate was calculated as follows by central laboratory:

pCR Rate = Number of patients with pCR / ITT population.

From the 83 patients registered, there were 2 patients that had not received any cycle and they were excluded of analysis by Intent To Treat (ITT) criterium: One patient did not receive any cycle, ended treatment by investigator´s criterium and the other patient withdrawn informed consent before starting the treatment.

The ORR was reported including a 95% confidence interval. The estimate of the ORR was determined according to RECIST 1.1 and measured by MRI and mammogram in patients treated with this regimen. ORR was calculated as follows:

Overall Response Rate = Number of Complete Responses (CRs), Partial Responses (PRs) / ITT population

From the 83 patients registered, there were 2 patients that had not received any cycle and they were excluded of analysis by Intent To Treat (ITT) criterium: One patient did not receive any cycle, ended treatment by investigator´s criterium and the other patient withdrawn informed consent before starting the treatment.

The ORR was reported including a 95% confidence interval. The estimate of the ORR was determined according to RECIST 1.1 and measured by MRI and mammogram in patients treated with this regimen. ORR was calculated as follows:

Overall Response Rate = Number of CRs, PRs / ITT population

From the 83 patients registered, there were 2 patients that had not received any cycle and they were excluded of analysis by Intent To Treat (ITT) criterium: One patient did not receive any cycle, ended treatment by investigator´s criterium and the other patient withdrawn informed consent before starting the treatment.

IDFS was defined as the time (days) from the date of randomization until the date of objective recurrent disease (local, regional or distant), second primary invasive malignancy (breast or non-breast) or death from any cause. For patients not known to have died as of the data cut-off date and who do not have recurrent disease or second primary tumor, invasive disease-free survival will be censored at the last contact date. Ductal carcinoma in-situ (DCIS) will not be considered an event for the purpose of this analysis.

From the 83 patients registered, there were 2 patients that had not received any cycle and they were excluded of analysis by Intent To Treat (ITT) criterium: One patient did not receive any cycle, ended treatment by investigator´s criterium and the other patient withdrawn informed consent before starting the treatment.

The conversion from the initially planned mastectomy to BCS was reported including a 95% confidence interval. The estimate of the rate of conversion to BCS was calculated as follows:

BCS rate = Number of patients with BCS / Number of patients with initially planned mastectomy.

From the 83 patients registered, there were 2 patients that had not received any cycle and they were excluded of analysis by Intent To Treat (ITT) criterium: One patient did not receive any cycle, ended treatment by investigator´s criterium and the other patient withdrawn informed consent before starting the treatment.

Mastectomy was de initial planned surgery for 50 patients.

Incidence of adverse events by maximum CTCAE grade (v4.03; NCI 2010) that occur during the study treatment period or within 30 days of the last dose of study treatment, regardless of causality and according to the relationship to study drug as assessed by the investigator, were collected and evaluated.

From the 83 patients registered, there were 2 patients that had not received any cycle and they were excluded of analysis by Intent To Treat (ITT) criterium: One patient did not receive any cycle, ended treatment by investigator´s criterium and the other patient withdrawn informed consent before starting the treatment.

Ki67 was analysed by immunohistochemistry following the American Society of Clinical Oncology and the College of American Pathologists guidelines. The cut-off considered for Ki67 expression was 20% of positively stained tumor cells.

Of the 81 patients, 77 had available pretreatment tumors for biomarker central analysis. Of these 77, 5 were excluded (3 due to Triple Negative (TN) phenotype, 1 due to missing pathological response data, and 1 due to incomplete central biomarker data). Ki67 was determined in 72 tumors and correlated to RCB (DOI: 10.1634/theoncologist.2017-0052)

Caveolin (Cav)-1 was evaluated in the stroma and its expression was categorized in low, moderate, or high (tertile). The high expression of Cav-1 was considered as positive.

83 patients registered, but 2 patients that had not received any cycle and they were excluded of analysis by Intent To Treat (ITT) criterium.

Of the 81 patients, 77 had available pretreatment tumors for biomarker central analysis. Of these 77, 5 were excluded (3 due to Triple Negative (TN) phenotype, 1 due to missing pathological response data, and 1 due to incomplete central biomarker data). Cav-1 was determined in 72 tumors and correlated to RCB (DOI: 10.1634/theoncologist.2017-0052)

SPARC was evaluated for both tumor and stroma. Its expression was categorized as negative when the intensity was absent-to-weak (1), or moderate (11)-to-strong (111) with a proportion of stained cells <10%. Immunolabeling was positive if the intensity was moderate (11)-to-strong (111) and the extent of staining was 10%.

83 patients registered, but 2 patients that had not received any cycle and they were excluded of analysis by Intent To Treat (ITT) criterium.

Of the 81 patients, 77 had available pretreatment tumors for biomarker central analysis. Of these 77, 5 were excluded (3 due to Triple Negative (TN) phenotype, 1 due to missing pathological response data, and 1 due to incomplete central biomarker data). SPARC was determined in 72 tumors and correlated to RCB (DOI: 10.1634/theoncologist.2017-0052)

Molecular subtypes were classified according to St. Gallen criteria 2013 and Prat et al. into Luminal A (ER+, Progesterone Receptor (PgR) >20%, Human Epidermal growth factor Receptor 2 - (HER2), Ki67 <14%), Luminal B1 (ER+, HER2-, PgR >20% and/or Ki67 <14%), Luminal B2 (ER+, HER2+, any PgR, any Ki67), TN (ER-, PgR-, HER2-), and HER2-enriched (ER-, PgR-, HER2+) subtypes.

83 patients registered, but 2 patients that had not received any cycle and they were excluded of analysis by Intent To Treat (ITT) criterium.

Of the 81 patients, 77 had available pretreatment tumors for biomarker central analysis. Of these 77, 5 were excluded (3 due to TN phenotype, 1 due to missing pathological response data, and 1 due to incomplete central biomarker data). Molecular subtypes was determined in 72 tumors and correlated to RCB (DOI: 10.1634/theoncologist.2017-0052)

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