Bevacizumab plus preoperative chemotherapy in operable HER2 negative breast cancer: biomarkers and pathologic response

Purpose: The primary aim of this trial was to assess the rate of pathologic complete responses (pCR) of doxorubicin/cyclophosphamide (AC) followed by bevacizumab/docetaxel (BT), as neoadjuvant therapy for breast cancer (BC). Furthermore, the association between biomarkers and the pCR was explored. Methods: Patients with HER-negative operable stage II–III BC ≥2 cm were enrolled. Four cycles of AC (A 60 mg/m2 and C 600 mg/m2, every 3 weeks) followed by 4 cycles of BT (B 15 mg/kg and T 75 mg/m2, every 3 weeks), were planned. A core-biopsy was performed for biological markers assessment. Results: Seventy-two women were included. Forty-three (63 %) patients were hormone receptor-positive. Sixty-four (89 %) completed the planned treatment, and 66 evaluable patients underwent surgery (92 %): a pCR was achieved in 16 of them (24, 95 % CI 15–36 %). pCR was significantly higher in tumors hormone receptor-negative, and in those with Angiotensin II type 1 receptor (AGTR1) protein overexpression. The overall clinical response rate was 86 % (95 % CI 76–93 %), including 42 complete responses. No unexpected toxicities or treatment-related deaths were observed. Conclusion: This regimen showed a remarkable clinical and pathological activity: the suggested relation between pCR and AGTR1 overexpression should be confirmed in larger trials.Financial support for this research was provided by Roche Farma, S.A

Health-related quality of life with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor–positive metastatic breast cancer: Patient-reported outcomes in the PEARL study

Background: The PEARL study showed that palbociclib plus endocrine therapy (palbociclib/ET) was not superior to capecitabine in improving progression-free survival in postmenopausal patients with metastatic breast cancer resistant to aromatase inhibitors, but was better tolerated. This analysis compared patient-reported outcomes. Patients and methods: The PEARL quality of life (QoL) population comprised 537 patients, 268 randomised to palbociclib/ET (exemestane or fulvestrant) and 269 to capecitabine. Patients completed the European Organisation for Research and Treatment of Cancer QLQC30 and QLQ-BR23 and EQ-5D-3L questionnaires. Changes from the baseline and time to deterioration (TTD) were analysed using linear mixed-effect and stratified Cox regression models, respectively. Results: Questionnaire completion rate was high and similar between treatment arms. Significant differences were observed in the mean change in global health status (GHS)/QoL scores from the baseline to cycle 3 (2.9 for palbociclib/ET vs.-2.1 for capecitabine (95% confidence interval [CI], 1.4-8.6; P = 0.007). The median TTD in GHS/QoL was 8.3 months for palbociclib/ET versus 5.3 months for capecitabine (adjusted hazard ratio, 0.70; 95% CI, 0.55-0.89; P = 0.003). Similar improvements for palbociclib/ET were also seen for other scales as physical, role, cognitive, social functioning, fatigue, nausea/vomiting and appetite loss. No differences were observed between the treatment arms in change from the baseline in any item of the EQ-5D-L3 questionnaire as per the overall index score and visual analogue scale. Conclusion: Patients receiving palbociclib/ET experienced a significant delay in deterioration of GHS/QoL and several functional and symptom scales compared with capecitabine, providing additional evidence that palbociclib/ET is better tolerated. Trial registration number: NCT02028507 (ClinTrials.gov). EudraCT study number: 2013-003170-27. 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Cáncer de mama: utilidad pronóstica de los Perfiles de Expresión Proteica en pacientes con tumor residual viable (>1.0cm.) tras Quimioterapia neoadyuvante

La identificació de marcadors moleculars en el tumor residual després de quimioteràpia neoadjuvant ( QTN ) en Càncer de Mama permet una millor caracterització pronostica . S'han seleccionat un total de 256 pacients amb QTN entre 1996 i 2011 , amb tumor residual ( > 1 cm ) . S'ha realitzat una matriu matricial de teixits i estudi inmunohistoquimic de l'expressió de 29 marcadors moleculars . L'anàlisi s'ha realitzat sobre l'aparició de metàstasi i la supervivència lliure de progressió a distància . El model multivariant ( mètode stepwise ) obté una signatura molecular amb sis marcadors de mal pronòstic : ER [ = 0 ] , cit - P65 [ 75 ] , cit - PTEN [ = 0 ] , BCL2 [ 20 ] . Una anàlisi en funció de l'expressió de receptors de estrògens identifica marcadors associats a mal pronòstic en RE -negatiu [ = 0 ] : ]: HER4-cit [>70] (p 0.01), P65-nuc [>37] (p 0.01), BP1 [>100] (p 0.001) p65-cit [80] (p 0.04) y GATA 3 [ 0 ] : Ciclina D1-nuc [>145] (p 0.02) Ki67 [>24] (p 0.02) Survivina-nuc [145] (p 0.03)La identificación de marcadores moleculares en el tumor residual tras quimioterapia neoadyuvante (QTN) en Cáncer de Mama permite una mejor caracterización pronostica. Se han seleccionado un total de 256 pacientes con QTN entre 1996 y 2011, con tumor residual (> 1 cm). Se ha realizado un array matricial de tejidos y estudio IHQ de la expresión de 29 marcadores moleculares. El análisis se ha realizado sobre la aparición de metástasis y la supervivencia libre de progresión a distancia. El modelo multivariante (método stepwise) obtiene una firma molecular con seis marcadores de mal pronóstico: ER [= 0], cit-P65 [ 75], cit-PTEN [= 0], BCL2 [ 20]. Un análisis en función de la expresión de RE identifica marcadores asociados a mal pronostico en RE-negativo [=0]: HER4-cit [>70] (p 0.01), P65-nuc [>37] (p 0.01), BP1 [>100] (p 0.001) p65-cit [80] (p 0.04) y GATA 3 [0]: Ciclina D1-nuc [>145] (p 0.02) Ki67 [>24] (p 0.02) Survivina-nuc [145] (p 0.03) .Identification of molecular markers in the residual tumor after neoadjuvant chemotherapy ( QTN ) in breast cancer allows better prognostic characterization . A total of a total of 256 patients between 1996 and 2011 QTN with residual tumor ( > 1 cm) have been selected . A tissue array and inmunohistochemistry study of expression of 29 molecular markers has been performed. The analysis was conducted on the occurrence of metastasis and progression-free survival distance. The multivariate model ( stepwise method ) obtained a molecular signature of six prognostic markers : ER [= 0] , cit - P65 [ 75 ] , cit - PTEN [= 0] , BCL2 [ 20 ] . An analysis based on the expression of estrogen receptor identifies markers associated with poor prognosis in ER - negative [= 0 ]: HER4-cit [>70] (p 0.01), P65-nuc [>37] (p 0.01), BP1 [>100] (p 0.001) p65-cit [80] (p 0.04) y GATA 3 [ 0 ] : Ciclina D1-nuc [>145] (p 0.02) Ki67 [>24] (p 0.02) Survivina-nuc [145] (p 0.03)

Limitations in predicting PAM50 intrinsic subtype and risk of relapse score with Ki67 in estrogen receptor-positive HER2-negative breast cancer

PAM50/Prosigna gene expression-based assay identifies three categorical risk of relapse groups (ROR-low, ROR-intermediate and ROR-high) in post-menopausal patients with estrogen receptor estrogen receptor-positive (ER+)/ HER2-negative (HER2-) early breast cancer. Low risk patients might not need adjuvant chemotherapy since their risk of distant relapse at 10-years is below 10% with endocrine therapy only. In this study, 517 consecutive patients with ER+/HER2- and node-negative disease were evaluated for Ki67 and Prosigna. Most of Luminal A tumors (65.6%) and ROR-low tumors (70.9%) had low Ki67 values (0-10%); however, the percentage of patients with ROR-medium or ROR-high disease within the Ki67 0-10% group was 42.7% (with tumor sizes ≤2 cm) and 33.9% (with tumor sizes > 2 cm). Finally, we found that the optimal Ki67 cutoff for identifying Luminal A or ROR-low tumors was 14%. Ki67 as a surrogate biomarker in identifying Prosigna low-risk outcome patients or Luminal A disease in the clinical setting is unreliable. In the absence of a well-validated prognostic gene expression-based assay, the optimal Ki67 cutoff for identifying low-risk outcome patients or Luminal A disease remains at 14%

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

International audienc