Management of Oligometastatic Breast Cancer: An Expert Committee's Opinion.

Patients with oligometastatic breast cancer (BC) are candidates of choice for metastasis-directed therapy (MDT). This paper summarizes the opinions of an expert committee about the management of oligometastatic BC. The experts could complete the questionnaire from 13 September 2021, to 10 October 2021, followed by a discussion. The experts were physicians working in the Province of Quebec (Canada) and specialized in BC care, including surgical oncologists, medical oncologists, and radiation oncologists. The experts provided their opinions about the context of the disease and therapeutic approach, local and systemic therapies, and the prognosis of oligometastatic BC. In addition to the expert panel's opinions about the management of oligometastatic disease per se, the experts stated that a prospective data registry should be implemented to collect data about oligometastatic BC to improve knowledge about oligometastatic BC and implement data-driven MDT. These data could also allow for the design of treatment algorithms. In conclusion, this paper presents the expert panel's opinions about the management of oligometastatic BC and highlights the needs to be met to improve the care of this condition.

HER2-positive breast cancer is lost in translation: time for patient-centered research.

No biomarker beyond HER2 itself, which suffers from a low positive predictive value, has demonstrated clinical utility in breast cancer, despite numerous attempts to improve treatment tailoring for the growing number of anti-HER2 targeted therapies. This prompted us to examine the body of evidence, using a systematic approach, to identify putative predictive biomarkers in HER2-positive breast cancer, and discuss the hitherto failure to address the needs of patients. In the future, it is hoped immune-based biomarkers will predict benefit from anti-HER2 treatments in the neoadjuvant and adjuvant settings. In advanced-stage disease, the quantification of tumour heterogeneity using molecular-imaging technology has generated informative data on the success or failure of the antibody-drug conjugate T-DM1. Treatment tailoring remains a high priority, in cost-constrained health-care systems, but such tailoring will require a dramatic shift in the way translational research is being conducted, with the establishment of large, easily accessible, and well-annotated databases of candidate predictive biomarkers. Single-centre biomarker research should become a thing of the past.

Regional Nodal Irradiation After Breast Conserving Surgery for Early HER2-Positive Breast Cancer: Results of a Subanalysis From the ALTTO Trial.

Background: Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown. Methods: This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). A multivariable cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timing was carried out to investigate the relationship between RNI and DFS. Results: One thousand six hundred sixty-four HER2-positive breast cancer patients were included, of whom 878 (52.8%) had received RNI to the axillary, supraclavicular, and/or internal mammary lymph nodes. Patients in the RNI group had higher nodal burden and more frequently had tumors larger than 2 cm. At a median follow-up of 4.5 years, DFS was 84.3% in the RNI group and 88.3% in the non-RNI group. No differences in regional recurrence (0.9 % vs 0.6 %) or in overall survival (93.6% vs 95.3%) were observed between the two groups. After adjustment in multivariable analysis, there was no statistically significant association between RNI and DFS (hazard ratio = 0.96, 95% confidence interval = 0.71 to 1.29). Conclusions: Our analysis did not demonstrate a DFS benefit of RNI in HER2-positive, node-positive patients treated with adjuvant HER2-targeted therapy. The benefit of RNI in HER2-positive breast cancer needs further testing within randomized clinical trials.

CCR 20th Anniversary Commentary: Gene-Expression Signature in Breast Cancer--Where Did It Start and Where Are We Now?

Desmedt and colleagues published two articles, one in the June 1, 2007 issue, and the other in the August 15, 2008, issue of Clinical Cancer Research, that showed gene-expression signatures to be proliferation driven and time dependent, with their prognostic power decreasing with increasing follow-up years. Moreover, the articles showed that immune response is a crucial determinant of prognosis in the HER2-positive and estrogen receptor-negative/HER2-negative subtypes, providing a rationale to further explore the role of the antitumor immune response in these breast cancer subtypes.

Immunology and breast cancer: toward a new way of understanding breast cancer and developing novel therapeutic strategies.

Every cancer triggers an immune response that constitutes an important first-line protection against cancer progression. In breast cancer, there is an increasing awareness of the relationship between the immune system and tumor evolution. The tumor microenvironment is composed of a variety of immune cells that can control or arrest malignant progression. Chemotherapy and targeted therapy have been shown to modulate this immune microenvironment. Recently, tumor-infiltrating lymphocytes have emerged as a predictive and prognostic biomarker in early breast cancer. In addition, immune gene expression signatures have been shown to be associated with prognosis in triple-negative and human epidermal growth factor receptor 2-positive breast cancer. Such findings have increased interest in the development of immunotherapeutic agents for breast cancer, and multiple clinical trials of anticancer vaccines and immune checkpoint inhibitors are ongoing. In this review, we summarize what is known about the relationship between immunity and breast carcinoma, explore the relevance of this information to the clinical and research settings, and give a portrait of new therapeutic strategies using immunotherapy in breast cancer.

Liquid biopsy: will it be the 'magic tool' for monitoring response of solid tumors to anticancer therapies?

PURPOSE OF REVIEW: The aim of this review is to highlight the recent advances (in the past 12 months) concerning circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in oncology. RECENT FINDINGS: The value of CTCs as a prognostic biomarker is now well validated in breast, colon, and prostate cancer, but no trial has yet demonstrated that modifying treatment according to CTCs is superior to standard of care. Ongoing trials are addressing the clinical utility of CTCs. Moreover, there is emerging evidence about the potential of CTCs as a tumor tissue source to analyze protein and RNA expression, DNA mutations and drug sensitivity. ctDNA is a specific biomarker associated with tumor burden, and small studies have shown an association with worse outcome; prospective clinical studies on the prognostic and predictive value of ctDNA are needed. ctDNA can be used for tumor molecular profiling, with the potential advantage to encompass the spectrum of mutations present in the tumor. SUMMARY: CTCs and ctDNA are promising new biomarkers in oncology, with potential clinical applications for monitoring and for comprehensive molecular profiling of cancer. For each assay, demonstration of analytical and clinical validity, as well as clinical utility in prospective clinical trials is needed before implementation in clinical practice.

Parental autonomy-support, intrinsic life goals, and well-being among adolescents in China and North America.

Self-determination theory proposes that prioritizing intrinsic life goals, such as community involvement, is related to well-being, whereas focusing on extrinsic life goals, such as financial success, is associated with lower well-being and that parenting influences the type of life goals that youth adopt. In a sample of 515 Chinese (56% female, mean age = 15.50) and 567 North American (52% male, mean age = 14.17) adolescents, a model of the relationships between parenting, life goals, and well-being was investigated and confirmed for intrinsic life goals. Across societies, autonomy-supportive parenting was associated with the endorsement of intrinsic life goals, which in turn was associated with well-being. Intrinsic life goals partially mediated the relationship between parental autonomy-support and well-being. These findings suggest that, cross-culturally, prioritizing intrinsic life goals is related to increased well-being among adolescents and that parents could encourage intrinsic life goals by being supportive of their children's autonomy.

Balance across contexts: importance of balanced need satisfaction across various life domains.

Self-determination theory posits that satisfaction of three basic psychological needs-autonomy, competence, and relatedness-are required for psychological well-being, and a recent study showed that the balance in the satisfaction of these three needs independently affects well-being. The present investigation builds on these findings by examining the balance of adolescents' need satisfaction across distinct life contexts. The results of three studies show that adolescents who experience a balance of need satisfaction across important life contexts, including at school, at home, with friends, and in part-time jobs, reported higher well-being and better school adjustment. This finding emerged consistently across four countries and across multiple measures of school adjustment, including teacher reports. Together, these results support previous research that highlights the importance of consistency for psychological functioning.