First-line therapy with palbociclib in patients with advanced HR+/HER2- breast cancer: The real-life study PALBOSPAIN.

PURPOSE: To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. METHODS: PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. RESULTS: A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse < 12 months after the end of ET, and 31 months (95% CI 26-37) and not reached (NR) in patients who experienced relapse > 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). CONCLUSION: These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. TRIAL REGISTRATION NUMBER: NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered.

Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer.

BACKGROUND: The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2-positive (HER2+) breast cancer. Here, we evaluated the association of HER2DX scores with (i) pCR according to hormone receptor status and various treatment regimens, and (ii) survival outcome according to pCR status. MATERIALS AND METHODS: Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n = 765) in combination with pertuzumab (n = 328), lapatinib (n = 187) or without a second anti-HER2 drug (n = 250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e. NEOHER and PAMELA) with a pCR (n = 118) and without a pCR (n = 150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low or high risk beyond pCR status. RESULTS: HER2DX pCR score was significantly associated with pCR in all patients [odds ratio (OR) per 10-unit increase = 1.59, 95% confidence interval 1.43-1.77; area under the ROC curve = 0.75], with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR = 2.36 (1.09-5.42). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR = 3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (P < 0.001) and OS (P = 0.006) compared with patients with HER2DX high-risk. CONCLUSIONS: HER2DX pCR score and risk score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.

Breast cancer PAM50 signature: correlation and concordance between RNA-Seq and digital multiplexed gene expression technologies in a triple negative breast cancer series.

BACKGROUND: Full RNA-Seq is a fundamental research tool for whole transcriptome analysis. However, it is too costly and time consuming to be used in routine clinical practice. We evaluated the transcript quantification agreement between RNA-Seq and a digital multiplexed gene expression platform, and the subtype call after running the PAM50 assay in a series of breast cancer patients classified as triple negative by IHC/FISH. The goal of this study is to analyze the concordance between both expression platforms overall, and for calling PAM50 triple negative breast cancer intrinsic subtypes in particular. RESULTS: The analyses were performed in paraffin-embedded tissues from 96 patients recruited in a multicenter, prospective, non-randomized neoadjuvant triple negative breast cancer trial (NCT01560663). Pre-treatment core biopsies were obtained following clinical practice guidelines and conserved as FFPE for further RNA extraction. PAM50 was performed on both digital multiplexed gene expression and RNA-Seq platforms. Subtype assignment was based on the nearest centroid classification following this procedure for both platforms and it was concordant on 96% of the cases (N = 96). In four cases, digital multiplexed gene expression analysis and RNA-Seq were discordant. The Spearman correlation to each of the centroids and the risk of recurrence were above 0.89 in both platforms while the agreement on Proliferation Score reached up to 0.97. In addition, 82% of the individual PAM50 genes showed a correlation coefficient > 0.80. CONCLUSIONS: In our analysis, the subtype calling in most of the samples was concordant in both platforms and the potential discordances had reduced clinical implications in terms of prognosis. If speed and cost are the main driving forces then the preferred technique is the digital multiplexed platform, while if whole genome patterns and subtype are the driving forces, then RNA-Seq is the preferred method.

Correction to: Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling.

In the original publication of the article, Table 1 was published with incorrect caption and values. The Table 1 with corrected caption and values is given in this Correction.

Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling.

BACKGROUND: Persistent alopecia (PA) after docetaxel has been recently described. The aim of our study is to establish the incidence and characteristics of PA following adjuvant docetaxel for breast cancer (BC) and to test the ability of scalp cooling in prevention. PATIENTS AND METHODS: BC patients receiving adjuvant chemotherapy followed or not by endocrine therapy (and a control group receiving only endocrine therapy) were interviewed in a single institution at 1.5 to 5 years following primary diagnosis searching for PA. A confirmatory prevalence study was later performed in other two institutions. Finally, a prevention study using prophylactic scalp cooling (PSC) with ELASTO-GEL hypothermia caps in patients receiving adjuvant docetaxel was performed. RESULTS: In the initial prevalence study (492 patients), minor forms of PA (grade 1) were recorded with all chemotherapy regimens and aromatase inhibitors. Patients receiving docetaxel regimens at cumulative dose (CD) ≥ 400 mmg/m2 presented a significantly higher prevalence of grades 1 PA (33-52%) and 2 PA (5-12%). Prevalence of grade 2 PA with docetaxel CD ≥ 400 mmg/m2 was confirmed in two other institutions. Overall, grade 2 PA was seen in 10.06% (95% CI 7.36-13.61) of 358 patients with docetaxel regimens reaching CD ≥ 400 mmg/m2, but not in patients with lower docetaxel CD, other chemotherapy regimens, or endocrine therapy alone. In prevention trial, no grade 2 PA occurred among 116 patients receiving adjuvant docetaxel (≥ 400 mmg/m2) and PSC followed-up after a 96 months median time. PSC was well tolerated. No scalp relapses were seen among 30 patients (22% of all inclusions) having disease relapse. CONCLUSION: Adjuvant treatment with docetaxel (CD ≥ 400 mmg/m2) is associated with a significant rate of grade 2 PA, leading to wearing a wig, in around 10% of patients. This toxicity was completely prevented with scalp cooling. Clinical Trial Reference: NCT00515762.

Five Years of Multidisciplinary Care in Hereditary Cancer: Our Experience in a Spanish University Hospital.

OBJECTIVE: To analyse the evolution of a multidisciplinary heredofamilial cancer unit (HFCU) in a university hospital. METHODS: This was a retrospective analysis of the activity of our HFCU in its first 5 years of existence. RESULTS: Between July 2010 and July 2015, 1,518 patients from 1,318 families attended our HFCU. Genetic testing was offered to 862 patients. Of those, 833 (96.6%) accepted testing, with available results for 636 (76.4%). Pathogenic mutations in BRCA1 and BRCA2 were found in 175 patients. Lynch syndrome and adenomatous polyposis were the most frequent syndromes diagnosed (151/175, 86.3%) among 17 different syndromes studied. Of the 404 patients without a previous genetic diagnosis in the family, 62 (15.3%) were found to have mutations in disease-causing genes. Prophylactic surgery and follow-up (33.7%) or follow-up only (66.3%) was proposed for mutation carriers according to international guidelines and patients' preferences. CONCLUSION: We have a high mutation detection rate, genetic test acceptance, and compliance with risk reduction strategies. However, there is room for improvement, especially in genetic testing timing, considering that an increase in the indications for genetic testing is expected.

Prospective, multicenter study on the economic and clinical impact of gene-expression assays in early-stage breast cancer from a single region: the PREGECAM registry experience.

INTRODUCTION: The aim of this study is to evaluate the cost-effectiveness and impact of gene-expression assays (GEAs) on treatment decisions in a real-world setting of early-stage breast cancer (ESBC) patients. METHODS: This is a regional, prospective study promoted by the Council Health Authorities in Madrid. Enrolment was offered to women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, node-negative or micrometastatic, stage I or II breast cancer from 21 hospitals in Madrid. Treatment recommendations were recorded before and after knowledge of tests results. An economic model compared the cost-effectiveness of treatment, guided by GEAs or by common prognostic factors. RESULTS: 907 tests (440 Oncotype DX® and 467 MammaPrint®) were performed between February 2012 and November 2014. Treatment recommendation changed in 42.6% of patients. The shift was predominantly from chemohormonal (CHT) to hormonal therapy (HT) alone, in 30.5% of patients. GEAs increased patients' confidence in treatment decision making. Tumor grade, progesterone receptor positivity and Ki67 expression were associated with the likelihood of change from CHT to HT (P < 0.001) and from HT to CHT (P < 0.001). Compared with current clinical practice genomic testing increased quality-adjusted life years by 0.00787 per patient and was cost-saving from a national health care system (by 13.867€ per patient) and from a societal perspective (by 32.678€ per patient). CONCLUSION: Using GEAs to guide adjuvant therapy in ESBC is cost-effective in Spain and has a significant impact on treatment decisions.

Review: circulating tumor cells in the practice of breast cancer oncology.

The primary cause of tumor-related death in breast cancer is still represented by distant metastasization. The dissemination of tumor cells from the primary tumor to distant sites through bloodstream cannot be early detected by standard imaging methods. Circulating tumor cells (CTCs) play a major role in the metastatic spread of breast cancer. Different analytical systems for CTCs isolation and detection have been developed and novel areas of research are directed towards developing assays for CTCs molecular characterization. This review describes the current state of art on CTCs detection techniques and the present and future clinical implications of CTCs enumeration and characterization.

Running away from side effects: physical exercise as a complementary intervention for breast cancer patients.

The number of breast cancer survivors increases every year, thanks to the development of new treatments and screening techniques. However, patients present with numerous side effects that may affect their quality of life. Exercise has been demonstrated to reduce some of these side effects, but in spite of this, few breast cancer patients know and follow the exercise recommendations needed to remain healthy. In this review, we describe the different breast cancer treatments and the related side effects and implications of exercise in relation to these. We propose that exercise could be an integrative complementary intervention to improve physiological, physical and psychological factors that affect survival and quality of life of these patients. For that reason, the main objective of this review is to provide a general overview of exercise benefits in breast cancer patients and recommendations of how to design exercise interventions in patients with different side effects.

SEOM clinical guidelines in metastatic breast cancer 2015.

Metastatic breast cancer is essentially an incurable disease. However, recent advances have resulted in a significant improvement of overall survival. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with metastatic breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference.