The role of modern parameters and their relationship with recurrence risk as assessed by Oncotype DX: real-world evidence.

Genomic analysis through various platforms is an essential tool for determining prognosis and treatment in a significant subgroup of early-stage breast cancer patients with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative status. Additionally, combined clinical and pathological characteristics can accurately predict the recurrence score (RS), as demonstrated by the University of Tennessee risk nomogram. In this study, we aimed to identify classical clinical-pathological factors associated with high RS in a local population, including modern parameters such as current abemaciclib treatment recommendations, HER2-low status, different Ki-67 cutoff values, and samples obtained from secondary primary tumours. This is a retrospective single-institution study that analysed a total of 215 tumour samples. Among lymph node-negative patients (n = 179), age, Ki67 values, and progesterone receptor status predicted RS after multivariate analysis. HER2-low status was not associated with RS differences (p = 0.41). Among lymph node-positive patients (n = 36), MonarchE inclusion criteria (15) were not associated with a higher RS (p = 0.61), and HER2-low did not reach statistical significance. However, tumours classified as secondary primaries numerically exhibited a higher RS. Based on these findings from our real-world sample, the mere application of clinical and pathological parameters is insufficient to predict RS outcomes. Modern parameters such as HER2-low status or adjuvant abemaciclib recommendations were not associated with RS differences. Regarding the observation of secondary tumours, more evidence is needed to understand whether prior hormone therapy exposure impacts the biological risk of secondary primary tumours.

The Emerging Role of Tertiary Lymphoid Structures in Breast Cancer: A Narrative Review.

This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, and prognostic value, and current ways of recognizing them. A comprehensive literature review was performed using the PubMed/Medline, Scopus, and EMBASE databases. A significant area of interest in breast cancer research involves targeting immune checkpoint molecules, particularly in the triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations in accurately predicting treatment response. In this context, tertiary lymphoid structures (TLSs) emerge as a prognostic biomarker and also as a promising predictive marker for response. TLSs are ectopic lymphoid formations or neo-organogenesis that can develop after prolonged exposure to inflammatory signals mediated by chemokines and cytokines. Their presence is inversely correlated with estrogen receptor (ER) and/or progesterone receptor (PR) expression, but positively associated with a higher pathologic complete response rate and improved overall survival. In certain scenarios, TLS-positive tumors were associated with improved outcomes regardless of the presence of PDL-1 (programmed cell death ligand 1) expression or TILs (tumor-infiltrating lymphocytes).

Systemic Treatment of Patients With Metastatic Breast Cancer: ASCO Resource-Stratified Guideline.

PURPOSE: To guide clinicians and policymakers in three global resource-constrained settings on treating patients with metastatic breast cancer (MBC) when Maximal setting-guideline recommended treatment is unavailable. METHODS: A multidisciplinary, multinational panel reviewed existing ASCO guidelines and conducted modified ADAPTE and formal consensus processes. RESULTS: Four published resource-agnostic guidelines were adapted for resource-constrained settings; informing two rounds of formal consensus; recommendations received ≥75% agreement. RECOMMENDATIONS: Clinicians should recommend treatment according to menopausal status, pathological and biomarker features when quality results are available. In first-line, for hormone receptor (HR)-positive MBC, when a non-steroidal aromatase inhibitor and CDK 4/6 inhibitor combination is unavailable, use hormonal therapy alone. For life-threatening disease, use single-agent chemotherapy or surgery for local control. For premenopausal patients, use ovarian suppression or ablation plus hormone therapy in Basic settings. For human epidermal growth factor receptor 2 (HER2)-positive MBC, if trastuzumab, pertuzumab, and chemotherapy are unavailable, use trastuzumab and chemotherapy; if unavailable, use chemotherapy. For HER2-positive, HR-positive MBC, use standard first-line therapy, or endocrine therapy if contraindications. For triple-negative MBC with unknown PD-L1 status, or if PD-L1-positive and immunotherapy unavailable, use single-agent chemotherapy. For germline BRCA1/2 mutation-positive MBC, if poly(ADP-ribose) polymerase inhibitor is unavailable, use hormonal therapy (HR-positive MBC) and chemotherapy (HR-negative MBC). In second-line, for HR-positive MBC, Enhanced setting recommendations depend on prior treatment; for Limited, use tamoxifen or chemotherapy. For HER2-positive MBC, if trastuzumab deruxtecan is unavailable, use trastuzumab emtansine; if unavailable, capecitabine and lapatinib; if unavailable, trastuzumab and/or chemotherapy (hormonal therapy alone for HR-positive MBC).Additional information is available at www.asco.org/resource-stratified-guidelines. It is ASCO's view that healthcare providers and system decision-makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Hormone Receptor-Positive / HER2-Negative Early Breast Cancer High-Risk Population: An Algorithm for Optimization Systemic Adjuvant Treatment Based on 2022 Updates.

Prognostic and predictive factors for early and late distant distance recurrence risk in estrogen-receptor positive and HER2-receptor negative early breast cancer are well known, but not all these variables work equally for the prediction. The following are the most widely accepted variables for categorizing risk levels: clinic-pathologic features (tumor size, lymph node involvement, histological grade, age, menopausal status, Ki-67 expression, estrogen, and progesterone expression), primary systemic treatment response (pathologic response and/or Ki-67 downstaging), and gene expression signatures stratification. Treatment guidelines from cancer societies and collaborative groups, online predict-tools, real-world data and experts' opinion recommends different adjuvant strategies (chemotherapy, endocrine therapy, ovarian suppression, olaparib, or abemaciclib) depending on the low (< 10%), intermediate (10%-20%) or high-risk of distance recurrence at least in the first 5 years. Multiple randomized prospective trials were updated in 2022, that evidence allow us to perform a stratification of risk in pre- and postmenopausal women with estrogen-receptor positive and HER2-receptor negative early breast cancer based on a combination of clinic-pathologic features and genomic assays and guide the adjuvant systemic treatment recommendation for those with high risk.

LuciA-15 - a real-world prospective study of PARP inhibitors for the treatment of patients with HER-2 negative metastatic breast cancer with germline and/or somatic mutation of BRCA genes or homologous recombination repair related genes.

Background: Poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) improve progression free survival among patients with HER2 negative (HER2-ve) advanced breast cancer (ABC) and a BRCA1 or BRCA2 mutation compared to chemotherapy (CT). The objective of this prospective study was to evaluate the clinical benefit of PARPi treatment in terms of response, outcomes and survival by breast cancer type and treatment in a Latin-American population. Methods: From September 2019 to April 2023, we analyzed the data of patients with HER2-ve ABC with germline and/or somatic mutation of BRCA1 or BRCA2, or in the homologous recombination repair genes, treated with olaparib or talazoparib in daily clinical practice by oncologist from Argentina and México. real-world objective response rate (rwORR), best response rate, real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were analysed with R software and RStudio version 14.0. Results: After a median follow-up of 18.07 months (95% CI 10.53-30.07), 51 patients were treated with PARPi. Mean age at starting treatment was 47.08 years. 62.7% had ER + ve/HER2-ve and 35.3% had triple negative breast cancer (TNBC). 62.7% and 37.3% of patients received talazoparib and olaparib, respectively. BRCA 1 and 2 germline mutations were the most common alterations found in 96% of patients. 37.5% of patients received platinum-based CT in the (neo)adjuvant/metastatic setting. At the time to starting PARPi treatment, 57.5% had visceral metastasis, the median number of metastatic sites was 2 (range 1-4), the median number of lines was 2 (range 0-8), and 23.5% and 31.4% received PARPi in the 1st line and 2nd line, respectively.The rwORR was 47.0%, and the median real-world progression-free survival-1 (rwPFS1) was 7.77 months (95% CI 5.67-14.7). There was a tendency of better rwPFS1 in patients with versus without previous CT in the advance setting, 6.37 months (95% CI 5.03-8.73) and 14.30 months (95% CI 6.47-NR), respectively (p 0.084). The median rwOS was 26.97 months (95% CI 13.50-NR) and higher in the subgroup of patients naïve for CT versus previous exposure to CT in the advance setting, the median rwOS was 32.1 months (95% CI 27.0-NR) versus 13.0 (95% CI10.1-NR), respectively (p 0.022). The medium real-world progression-free survival-2 (next treatment after PARPi failure) was 4.00 months (95% CI 3.43-7.13). Treatment was discontinued due to adverse events in 4.0% of patients. Conclusion: This is the first evidence in a Latin-American population that replicates the data already published in randomised clinical trials and other scanty real-world evidence studies in this field, showing positive results in rwORR and rwPFS, and encouraging data in rwOS. Notably, there was a high proportion of patients with visceral progression even with visceral crisis and need for CT. Interestingly, there were similar rwOS results among subgroups (TNBC versus ER + ve/HER2-ve, talazoparib versus olaparib, etc).

Precision medicine in the real-world setting. Clinical activity of talazoparib in a woman with hormone receptor-positive HER2-negative metastatic breast cancer with pathogenic mutation in somatic BRCA2.

Background: Next-generation sequencing (NGS) has proven to be a key implementation to understanding biological pathways involved in cancer. In daily practice, the identification of somatic and germline mutations has allowed physicians to gather relevant information to make therapeutic decisions and benefit patients. Importantly, somatic mutations provide targeted opportunities for treatment and reveal resistance mechanisms to understand patients' tumour evolution. Scanty data in clinical trials and in a real-world setting is available regarding the utility of poly(ADP-ribose) polymerase inhibitors in pathogenic or likely-pathogenic somatic breast cancer gene 1/2 (BRCA1/2) mutations and/or germline or somatic Homologous Recombination-Related Gene mutations in advanced breast cancer (ABC). Case report: Here we report a real-life case of a 47-year-old postmenopausal woman with hormone receptor-positive (HR-positive) Epidermal growth factor receptor 2 (HER2)-negative metastatic BC that had poor response to classic therapeutic strategies for HR+/HER2- ABC. At this point, the possibility of using NGS to guide the treatment was decided in a Molecular Tumour Board (MTB), and the patient had a major response to talazoparib targeting a non-germline BRCA2 mutation. Conclusion: Undoubtedly, more information regarding the cost effectiveness of NGS is needed to develop adequate reimbursement policies for this technology. It should be highlighted that the generalisation of MTBs and the implementation of molecular screening programmes are greatly needed in our region to gain more knowledge of somatic mutations implicated in the Hispanic and Latin-American population with BC diagnosis. Recently presented results of randomised studies may support the evaluation of somatic mutations with NGS to find targeted therapies for ABC patients.

Knowledge, Practice, and Attitudes of Physicians in Low- and Middle-Income Countries on Fertility and Pregnancy-Related Issues in Young Women With Breast Cancer.

PURPOSE: Fertility and pregnancy-related issues are highly relevant for young (≤ 40 years) patients with breast cancer. Limited evidence exists on knowledge, practice, and attitudes of physicians from low- and middle-income countries (LMICs) regarding these issues. METHODS: A 19-item questionnaire adapted from an international survey exploring issues about fertility preservation and pregnancy after breast cancer was sent by e-mail between November 2019 and January 2020 to physicians from LMICs involved in breast cancer care. Descriptive analyses were performed. RESULTS: A total of 288 physicians from Asia, Africa, America, and Europe completed the survey. Median age was 38 years. Responders were mainly medical oncologists (44.4%) working in an academic setting (46.9%). Among responders, 40.2% and 53.8% reported having never consulted the available international guidelines on fertility preservation and pregnancy after breast cancer, respectively. 25.0%, 19.1%, and 24.3% of responders answered to be not at all knowledgeable about embryo, oocyte, or ovarian tissue cryopreservation, respectively; 29.2%, 23.6%, and 31.3% declared that embryo, oocyte, and ovarian tissue cryopreservation were not available in their countries, respectively. 57.6% of responders disagreed or were neutral on the statement that controlled ovarian stimulation can be considered safe in patients with breast cancer. 49.7% and 58.6% of responders agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence overall or only in those with hormone receptor-positive disease, respectively. CONCLUSION: This survey showed suboptimal knowledge, practice, and attitudes of physicians from LMICs on fertility preservation and pregnancy after treatment completion in young women with breast cancer. Increasing awareness and education on these aspects are needed to improve adherence to available guidelines and to promote patients' oncofertility counseling.

Use of real-world evidence for oncology clinical decision making in emerging economies.

Real-world evidence (RWE) can provide insights into patient profiles, disease detection, treatment choice, dosing strategies, treatment sequencing, adverse event management and financial toxicity associated with oncology treatment. However, the full potential of RWE is untapped in emerging economies due to structural and behavioral factors. Structural barriers include lack of regulatory engagement, real-world data availability, quality and integrity. Behavioral barriers include entrenched healthcare professional behaviors that impede rapid RWE understanding and adoption. These barriers can be addressed with close collaboration of healthcare stakeholders; of whom, regulators need to be at the forefront given their ability to facilitate use of RWE in healthcare policy and legislation.

Lay abstract Traditionally, randomized clinical trials have been used to provide insights on new medical therapies and continue to remain the gold standard for approval. The-increasing availability of patient level data in the real-world, it is now possible to generate evidence regarding the usage and potential benefits or risks of a medical therapy derived from analysis of real-world data. This evidence is collectively referred to real-world evidence (RWE). randomized clinical trials and RWE are complementary and the area of Oncology especially benefits from RWE to guide clinical decision making across the patient journey. Key benefits include cancer screening and diagnosis, optimal treatment choices (including personalized medicine) and disease management such as dosing and treatment of side effects. In recent times, RWE generation in oncology has been prolific in the USA and western Europe. With expansive biopharmaceutical investments into infrastructure harnessing patient-level data and greater local regulatory guidance, oncology patients in emerging economies may now also have the opportunity to benefit from clinical decision making informed by RWE.

Implementation of a molecular tumour board in LATAM: the impact on treatment decisions for patients evaluated at Instituto Alexander Fleming, Argentina.

BACKGROUND: The role of the molecular tumour board (MTB) is to recommend personalised therapy for patients with cancer beyond standard-of-care treatment. A comprehensive molecular analysis of the tumour in a molecular pathology laboratory is important for all targeted therapies approaches. Here we report the 1-year experience of the Instituto Alexander Fleming Molecular Tumour Board. PATIENTS AND METHODS: The MTB of the Instituto Alexander Fleming was launched in December 2019 in a monthly meeting. In each interactive monthly session, five cases were presented and discussed by the members. These cases were referred by the treating oncologists. The MTB recommendations were sent to each physician individually, and to the rest of the meeting participants. This was discussed with the patients/families by the treating oncologist. The final decision to choose therapy was left to the treating physicians. Of the 32 patients presented at MTB, 28 (87.5%) had potentially actionable alterations and only 4 (12.5%) had no actionable mutation. Six (19%) patients received a local regulatory agency approved drug recommendation, nine (28%) patients received an off-label approval treatment recommendation and three (9%) patients did not receive the treatment due to access and reimbursement of the drug. CONCLUSION: In most of the cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. Molecular-guided extended personalised patient care is effective for a small but clinically significant proportion of patients in challenging clinical situations. We believe that the implementation of a MTB is feasible in the Latin America (LATAM) region.

Erratum: RENATA study-Latin American prospective experience: clinical outcome of patients treated with palbociclib in hormone receptor-positive metastatic breast cancer-real-world use.

[This corrects the article on p. 1 in vol. 14.].

RENATA study-Latin American prospective experience: clinical outcome of patients treated with palbociclib in hormone receptor-positive metastatic breast cancer-real-world use.

BACKGROUND: In hormone receptor-positive, HER-2 negative (HR+/HER2-) advanced breast cancer (ABC) endocrine therapy (ET) plus cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in first and second line improved progression-free survival (PFS), overall response rate (ORR) and clinical benefit rate (CB) without deterioration in quality of life compared with ET alone. In addition, recent data showed improvement in overall survival (OS) for premenopausal women in first line setting and for different subgroups of patients in second line. Since 2015, in Argentina, the combination of ET with CDK4/6i is a standard of care in HR+/HER2- ABC. METHODS: We carried out a prospective analysis of real-world use of palbociclib with ET in HR+/HER2- ABC patients who received treatment between October 2015 and August 2019 in two private institutes from Buenos Aires, Argentina. The aims of the study were to determine efficacy and safety of patients treated with ET and palbociclib, describe patient profile and treatment strategy beyond progression. RESULTS: One-hundred and twenty-eight patients were included in the final analysis. Main baseline characteristics include, median age 57 years, 20% were premenopausal women, 44% had visceral metastasis and 26% bone only disease. More than half of patients had two or more metastatic sites, 44.4% had performance status 1, and most of them (59.4%) were treated with palbociclib in first-line setting. Palbociclib was preferentially associated with aromatase inhibitors in 63.9% of patients, and with fulvestrant in the remaining. All premenopausal women received ovarian suppression or ovarian ablation (OS/OA). The median PFS was 36.7 months in first line and 24.2 months in second line. The ORR was 45.3% and 25.0% in first and second line, respectively. The median OS in the entire population was not reached. Half of patients did not require dose interruption and/or delay, dose reduction was required in 15% of patients and almost no patients required drug discontinuation (2.0%). With regard to safety, 55% of patients developed grade 3-4 adverse events, 20% neutropenia grade 3-4, and 7% febrile neutropenia. Infections were presented in one out of three patients, mostly uncomplicated. CONCLUSIONS: This is the first prospective evidence of real-world use of palbociclib in a Latin American population. We found similar outcomes to the PALOMA-2 and PALOMA-3 randomised trials and Real-World Data already published, with lower incidence of side effects and treatment discontinuation, but with higher incidence of febrile neutropenia.

[Chylopericardium and bilateral chylothorax in a breast cancer patient]. / Quilopericardio y quilotórax bilateral en una mujer con cáncer de mama.

Non traumatic chylopericar dium is mostly secondary to infection, congenital or neoplastic disease that invade mediastinal lymph nodes and modify the normal lymphatic flow. It is associated to chylothorax in approximately 3% of cases. We report the case of a 52 years old woman with diagnosis of advanced breast cancer. She was admitted with bilateral pleural effusion and echocardiographic signs of cardiac tamponade. A CT scan disclosed multiple mediastinal lymphadenopathy. The level of tryglicerides in pleural effusion was 372 mg/dl. A percutaneous pericardiocentesis was performed, obtaining chyle, with 984 mg/dl of tryglicerides and cholesterol 90 mg/dl levels. Treatment strategy was modified. We reviewed pathophysiology, diagnostic criteria and treatment of this rare entity.

Quilopericardio y quilotórax bilateral en una mujer con cáncer de mama / Chylopericardium and bilateral chylothorax in a breast cancer patient

El quilopericardio no traumático suele deberse a enfermedades infecciosas, congénitas o neoplásicas que infiltran los ganglios mediastinales, alteran el flujo linfático normal y acumulan quilo en la cavidad pericárdica. Se asocia a quilotórax en, aproximadamente, un 3% de los casos. Se presenta el caso de una paciente de 52 años con cáncer de mama avanzado que ingresa con derrame pleural bilateral y signos ecocardiográficos de taponamiento cardíaco. La TC mostró múltiples adenopatías en mediastino. El dosaje de triglicéridos en líquido pleural fue 372 mg/ dl. Por pericardiocentesis se obtuvo un líquido lechoso con triglicéridos de 984 mg/dl y colesterol 90 mg/dl. Se modificó el esquema terapéutico. Se revisan la fisiopatología, los criterios diagnósticos y el tratamiento de esta rara entidad.

Non traumatic chylopericar dium is mostly secondary to infection, congenital or neoplastic disease that invade mediastinal lymph nodes and modify the normal lymphatic flow. It is associated to chylothorax in approximately 3% of cases. We report the case of a 52 years old woman with diagnosis of advanced breast cancer. She was admitted with bilateral pleural effusion and echocardiographic signs of cardiac tamponade. A CT scan disclosed multiple mediastinal lymphadenopathy. The level of tryglicerides in pleural effusion was 372 mg/dl. A percutaneous pericardiocentesis was performed, obtaining chyle, with 984 mg/dl of tryglicerides and cholesterol 90 mg/dl levels. Treatment strategy was modified. We reviewed pathophysiology, diagnostic criteria and treatment of this rare entity.

Quilopericardio y quilotórax bilateral en una mujer con cáncer de mama / Chylopericardium and bilateral chylothorax in a breast cancer patient

El quilopericardio no traumático suele deberse a enfermedades infecciosas, congénitas o neoplásicas que infiltran los ganglios mediastinales, alteran el flujo linfático normal y acumulan quilo en la cavidad pericárdica. Se asocia a quilotórax en, aproximadamente, un 3% de los casos. Se presenta el caso de una paciente de 52 años con cáncer de mama avanzado que ingresa con derrame pleural bilateral y signos ecocardiográficos de taponamiento cardíaco. La TC mostró múltiples adenopatías en mediastino. El dosaje de triglicéridos en líquido pleural fue 372 mg/ dl. Por pericardiocentesis se obtuvo un líquido lechoso con triglicéridos de 984 mg/dl y colesterol 90 mg/dl. Se modificó el esquema terapéutico. Se revisan la fisiopatología, los criterios diagnósticos y el tratamiento de esta rara entidad.(AU)

Non traumatic chylopericar dium is mostly secondary to infection, congenital or neoplastic disease that invade mediastinal lymph nodes and modify the normal lymphatic flow. It is associated to chylothorax in approximately 3% of cases. We report the case of a 52 years old woman with diagnosis of advanced breast cancer. She was admitted with bilateral pleural effusion and echocardiographic signs of cardiac tamponade. A CT scan disclosed multiple mediastinal lymphadenopathy. The level of tryglicerides in pleural effusion was 372 mg/dl. A percutaneous pericardiocentesis was performed, obtaining chyle, with 984 mg/dl of tryglicerides and cholesterol 90 mg/dl levels. Treatment strategy was modified. We reviewed pathophysiology, diagnostic criteria and treatment of this rare entity.(AU)

Quilopericardio y quilotórax bilateral en una mujer con cáncer de mama. / [Chylopericardium and bilateral chylothorax in a breast cancer patient].

Non traumatic chylopericar dium is mostly secondary to infection, congenital or neoplastic disease that invade mediastinal lymph nodes and modify the normal lymphatic flow. It is associated to chylothorax in approximately 3

of cases. We report the case of a 52 years old woman with diagnosis of advanced breast cancer. She was admitted with bilateral pleural effusion and echocardiographic signs of cardiac tamponade. A CT scan disclosed multiple mediastinal lymphadenopathy. The level of tryglicerides in pleural effusion was 372 mg/dl. A percutaneous pericardiocentesis was performed, obtaining chyle, with 984 mg/dl of tryglicerides and cholesterol 90 mg/dl levels. Treatment strategy was modified. We reviewed pathophysiology, diagnostic criteria and treatment of this rare entity.