Neoadjuvant anthracycline-based (5-FEC) or anthracycline-free (docetaxel/carboplatin) chemotherapy plus trastuzumab and pertuzmab in HER2 + BC patients according to their TOP2A: a multicentre, open-label, non-randomized phase II trial.

Purpose: Previous studies have reported the benefit of dual HER2-targeting combined to neoadjuvant chemotherapy in HER2-amplified breast cancer (HER2 + BC). Moreover, besides the cardiac toxicity following their association to Trastuzumab, anthracyclines chemotherapy may not profit all patients. The NeoTOP study was designed to evaluate the complementary action of Trastuzumab and Pertuzumab, and the relevance of an anthracycline-based regimen according to TOP2A amplification status.

Breast-cancer detection using blood-based infrared molecular fingerprints.

Background: Breast cancer screening is currently predominantly based on mammography, tainted with the occurrence of both false positivity and false negativity, urging for innovative strategies, as effective detection of early-stage breast cancer bears the potential to reduce mortality. Here we report the results of a prospective pilot study on breast cancer detection using blood plasma analyzed by Fourier-transform infrared (FTIR) spectroscopy - a rapid, cost-effective technique with minimal sample volume requirements and potential to aid biomedical diagnostics. FTIR has the capacity to probe health phenotypes via the investigation of the full repertoire of molecular species within a sample at once, within a single measurement in a high-throughput manner.

Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy and anti-EGFR antibodies.

To find metastatic recurrence biomarkers of triple-negative breast cancer (TNBC) treated by neoadjuvant chemotherapy and anti-EGFR antibodies (NAT), we evaluated tumor genomic, transcriptomic, and immune features, using MSK-IMPACT assay, gene arrays, Nanostring technology, and TIL assessment on H&E. Six patients experienced a rapid fatal recurrence (RR) and other 6 had later non-fatal recurrences (LR). Before NAT, RR had low expression of 6 MHC class I and 13 MHC class II genes but were enriched in upregulated genes involved in the cell cycle-related pathways.

Response to Induction Neoadjuvant Hormonal Therapy Using Upfront 21-Gene Breast Recurrence Score Assay-Results From the SAFIA Phase III Trial.

Purpose: Luminal, human epidermal growth factor receptor 2-negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT).

Materials And Methods: The SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2-negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo.

Fluctuation of the left ventricular ejection fraction in patients with HER2-positive early breast cancer treated by 12 months of adjuvant trastuzumab.

Background: Cardiac toxicity with a decrease of the left ventricular ejection fraction (LVEF) is the main side effect induced by trastuzumab. This study reports the fluctuation of LVEF over the 12 months of adjuvant trastuzumab in PHARE trial (NCT00381901).

Methods: LVEF assessment was performed every 3 months while patients received trastuzumab and after completion of treatment over the first 2 years and then every 6 months afterwards.

Main implications related to the switch to 1/2 tumor testing in ovarian cancer patients: a proposal of a consensus.

Background: Since the approval of the first poly (adenosine diphosphate [ADP]) ribose polymerase inhibitor (PARPi; olaparib [Lynparza™]) for platinum-sensitive relapsed high grade ovarian cancer, with either germline or somatic deleterious variants, the strategies for are dynamically changing. Along with germline testing within the context of familial or sporadic ovarian cancer, patients are now being referred for genetic assay above all for treatment decisions: in this setting tumour BRCA assay can allow to identify an estimated 3-9% of patients with peculiar somatic mutations. These women could also benefit from PARPi therapy.

Predictive and prognostic significance of CD8 tumor-infiltrating lymphocytes in patients with luminal B/HER 2 negative breast cancer treated with neoadjuvant chemotherapy.

The immunobiology of breast cancer (BC) subtypes, including luminal cancer, remains unclear. Cluster of differentiation (CD)8 tumor-infiltrating lymphocytes (TIL) are essential components of tumor-specific cellular adaptive immunity. However, only few studies have addressed the significance of cluster of differentiation 8(CD8) TIL in patients with luminal BC.

Triple Negative Breast Cancer: A Tale of Two Decades.

Triple negative breast cancer (TNBC) is a heterogeneous disease entity constituting about 15% of breast cancer cases worldwide. TNBC is associated with poor prognosis and lack of sustained response to conventional chemotherapeutic agents. Tumoral heterogeneity and the presence of several subtypes of TNBC such as Basal like (BL)-1, BL-2, immune-modulatory, luminal androgen receptor, mesenchymal, and mesenchymal/stem like subtype and claudin low subtype, may explain some of the difficulties faced in managing this challenging disease subgroups.

Afatinib alone or afatinib plus vinorelbine versus investigator's choice of treatment for HER2-positive breast cancer with progressive brain metastases after trastuzumab, lapatinib, or both (LUX-Breast 3): a randomised, open-label, multicentre, phase 2 trial.

Background: Patients with advanced HER2-positive breast cancer frequently develop CNS metastases. The metastases that progress after brain radiotherapy and HER2-targeted systemic therapy are a difficult therapeutic challenge. We aimed to assess the efficacy and safety of afatinib, an irreversible blocker of the ErbB protein family, alone or combined with vinorelbine, compared with treatment of the investigator's choice in women with HER2-positive breast cancer with progressive brain metastases during or after treatment with trastuzumab, lapatinib, or both.

Cardiac toxicity events in the PHARE trial, an adjuvant trastuzumab randomised phase III study.

Background: This article reports, the cardiac toxicity according to 6- versus 12-month durations of adjuvant trastuzumab in PHARE randomised trial (NCT00381901).

Patients And Methods: Cardiac follow-up and Left Ventricular Ejection Fraction (LVEF) assessment by echocardiography or multigated acquisition scan were performed every 3 months while patients received trastuzumab and after completion of treatment over the first 2 years and every 6 months afterwards. The primary cardiac end-point was Cardiac Heart Failure (CHF) defined as New York Heart Association (NYHA) class III or IV.

Can pathologic complete response (pCR) be used as a surrogate marker of survival after neoadjuvant therapy for breast cancer?

Breast cancer is heterogeneous in clinical, morphological, immunohistochemical and biological features, as reflected by several different prognostic subgroups. Neoadjuvant approaches are currently used for the "in vivo" efficacy assessment of treatments. Pathological complete response (pCR) has been reported as a reliable predictive factor of survival in that setting.

[Node negative breast cancer. Beyond international consensus: a pragmatic approach].

Apart from therapeutic advances related to new treatments, our practices in the management of early breast cancer have been modified by to key organizational settings (1) mass screening, substantially altering the presentation and epidemiology of breast cancer and (2) the development of guidelines to ensure that any patient management is in agreement with the demonstrated impact in the adjuvant treatment. In daily practice, the impact of screening and guidelines recommendations has put us now in a paradoxical situation: while the majority of non-metastatic breast cancers treated in the hexagon are node negative, most of the results of clinical studies on chemotherapy and targeted therapies today arise from populations predominantly node positive. Therefore, it seemed legitimate to convene a working group around a reflection on the directions of adjuvant chemotherapy in a growing node negative population in order to better respond to the questions of the field oncologists, trying to address the discrepancies between different existing guidelines.

Estrogen receptor expression and docetaxel efficacy in patients with metastatic breast cancer: a pooled analysis of four randomized trials.

Background: Differences in the efficacy of various chemotherapies in patients with estrogen receptor (ER)(+) metastatic breast cancer are not well understood. In the present study, we assessed the efficacy of docetaxel in patients with metastatic breast cancer according to ER expression.

Methods: The efficacy of docetaxel in terms of the response rate and progression-free survival (PFS) time was analyzed according to ER expression in four randomized trials comparing a docetaxel-based regimen with a nontaxane regimen that included a total of 1,631 patients.

Role of aromatase inhibitors in the upfront adjuvant hormonal therapy of postmenopausal patients with breast cancer.

Tamoxifen has been considered for several decades as the standard upfront hormonal therapy for patients with endocrine-sensitive early breast cancer. The efficacy and favorable toxicity profiles of third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, in advanced disease led to their development in early breast cancer. Recent trial results consistently showed the superiority of AIs over tamoxifen in using the two following therapeutic approaches: either the upfront strategy (randomization of newly diagnosed patients: tamoxifen for 5 years vu AI for 5 years) or the sequencial strategy (randomization of newly diagnosed patients: tamoxifen (2-3 years) followed by AI or the inverse for a total of 5 years vs upfront AI for 5 years).

Does regional lymph node irradiation improve the outcome of N0 and pN0 breast cancer?

This study compares the outcome of 76 patients with N0 breast carcinoma, node-negative at axillary lymph node dissection (pN0) after neoadjuvant chemotherapy (NeoCT), treated with (RLNI+, 39 patients) or without (RLNI-, 37 patients) elective regional lymph node areas irradiation. For RLNI- and RLNI+ groups respectively at 10 years, survival without local-regional recurrence was 95% and 91% (p = .59), survival without distant metastasis was 97% and 78% (p = .

Comparative review of anastrozole, letrozole and exemestane in the management of early breast cancer.

The hormonal therapy of patients with endocrine-sensitive early breast cancer has mainly consisted, for several decades, of the gold standard tamoxifen. The efficacy and favorable toxicity profiles of third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, in advanced disease led to their development in early breast cancer. Recent results consistently show the superiority of these agents over tamoxifen.

Long-term safety of aromatase inhibitors in the treatment of breast cancer.

Following promising data for metastatic breast cancer in terms of efficacy and safety profile, third-generation aromatase inhibitors (AI), anastrozole, letrozole, and exemestane, underwent a full development in early setting. If recent results consistently show the superiority of these agents over tamoxifen, the therapeutic strategies of AIs in adjuvant setting are still debated. Beyond the choice of clinical strategy, the long duration of exposure to AI in adjuvant setting required a full determination of the long-term toxicity profile of these agents.

The emerging role of aromatase inhibitors in the adjuvant management of breast cancer.

Adjuvant hormonal therapy for patients with endocrine sensitive breast cancer has been dominated for several decades by the gold standard tamoxifen. Promising data on third generation aromatase inhibitors (AI), anastrozole, letrozole and exemestane, in metastatic setting led to the development of these agents in early breast cancer. If recent results consistently show the superiority of these agents over tamoxifen, the therapeutic strategies of AIs in adjuvant setting remain discussed.

Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer.

Purpose: Overall survival (OS) can be observed only after prolonged follow-up, and any potential effect of first-line therapies on OS may be confounded by the effects of subsequent therapy. We investigated whether tumor response, disease control, progression-free survival (PFS), or time to progression (TTP) could be considered a valid surrogate for OS to assess the benefits of first-line therapies for patients with metastatic breast cancer.

Patients And Methods: Individual patient data were collected on 3,953 patients in 11 randomized trials that compared an anthracycline (alone or in combination) with a taxane (alone or in combination with an anthracycline).

Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer.

Purpose: Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival.

Patients And Methods: Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines.

Cardiovascular safety profiles of aromatase inhibitors : a comparative review.

Third-generation aromatase inhibitors (AIs) are now being used for the adjuvant treatment of postmenopausal women with breast cancer, and are challenging tamoxifen, the previous 'gold standard' of care, in this setting. This review evaluates the potential clinical impact of anastrozole, letrozole and exemestane on the cardiovascular (CV) system of postmenopausal women with breast cancer. Some data for CV safety are available for AIs from the advanced disease setting; however, most derive from patients being treated for early disease.

Impact of chemotherapy regimens prior to endocrine therapy: Results from the ATAC (Anastrozole and Tamoxifen, Alone or in Combination) trial.

Background: The 33-month median follow-up of the ATAC (anastrozole and tamoxifen, alone or in combination) trial showed a potential interaction between anastrozole and previous chemotherapy; however, this was much smaller at 47 months' median follow-up. When the effects of different chemotherapy regimens were evaluated at that time, the apparent interaction was limited to patients who had received cyclophosphamide, methotrexate, and 5-fluorouracil (CMF).

Methods: In this retrospective analysis of 68-month data, we investigated the impact of prior chemotherapy, including different chemotherapy regimens, on time to recurrence.

Role of anastrozole across the breast cancer continuum: from advanced to early disease and prevention.

Breast tumorigenesis is a continuum from preinvasive lesions to early breast cancer and advanced disease. In this article the data supporting the use of the aromatase inhibitor anastrozole in postmenopausal women across this continuum are reviewed. In advanced disease, anastrozole has a significant survival benefit and tolerability advantage compared with megestrol acetate when used as second-line treatment.

Taxane therapy for early stage breast cancer.

Breast cancer is the most frequent cancer of women in developed countries. Systemic adjuvant chemotherapy has dramatically improved the outcome of patients treated for early stage invasive breast cancer. Among novel chemotherapeutic agents, the taxanes have emerged as the most powerful compounds since anthracycline regimens.