Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%-70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data.

Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer.

Although breast cancer is rare and understudied in adults age 40 and younger, recent epidemiologic data show an increasing incidence of breast cancer among young women in the United States and ongoing inferior long-term outcomes. Given breast cancers arising at a young age are more likely to present at advanced stages and to have aggressive biology, multimodal treatments are often indicated. Elevated local recurrence risks and greater propensity for germline cancer predisposition mutations can impact local therapy choices. Recently, escalated systemic therapy regimens for triple-negative breast cancer incorporating immunotherapy, de-escalated anti-HER2 therapy, and emerging targeted agents, including CDK4/6 inhibitors and PARP inhibitors, for early-stage disease may be employed in younger and older patients alike, with some special considerations. Prognostic genomic signatures can spare low-risk young women with hormone receptor-positive breast cancer adjuvant chemotherapy, but management of intermediate-risk patients remains controversial. Ovarian function suppression and extended endocrine therapy are improving outcomes in hormone receptor-positive breast cancer, but treatment adherence is a particular problem for young patients. Young women may also face greater challenges in long-term survivorship, including impaired fertility, difficulties in psychosocial adjustment, and other treatment-related comorbidities. Consideration of these age-specific issues through dedicated multidisciplinary strategies is necessary for optimal care of young women with breast cancer. 

Treatment of Breast Cancer in Young Adults

Simple Summary Poly-adenosine diphosphate ribose polymerase (PARP) inhibitors (PARPi) are effective against tumors with mutations in DNA repair genes, most commonly in the BRCA1 and BRCA2 genes. Because these tumors are unable to repair their DNA, PARPi have been used to target DNA repair pathways and are useful in the treatment of breast cancers with some of these alterations. There are two FDA-approved PARPi for patients with breast cancer—olaparib and talazoparib. The data on olaparib and talazoparib in the treatment of breast cancer are summarized in this review, and we also explore potential future applications of PARPi beyond inherited BRCA mutations. Abstract Poly-adenosine diphosphate ribose polymerase (PARP) inhibitors (PARPi) are approved for BRCA1/2 carriers with HER2-negative breast cancer in the adjuvant setting with a high risk of recurrence as well as the metastatic setting. However, the indications for PARPi are broader for patients with other cancer types (e.g., prostate and ovarian cancer), involving additional biomarkers (e.g., ATM, PALB2, and CHEK) and genomic instability scores. Herein, we summarize the data on PARPi and breast cancer and discuss their use beyond BRCA carriers.

/pdf/parp-inhibitors-for-breast-cancer-germline-brca1-2-and-1ts673r4.pdf

PARP Inhibitors for Breast Cancer: Germline BRCA1/2 and Beyond

Management of patients with early-stage triple-negative breast cancer following pembrolizumab-based neoadjuvant therapy: What are the evidences?

​Background Immunotherapy for lung cancer has been a hot research area for years. This bibliometric analysis aims to present the research trends on lung cancer immunotherapy. Method On 1 July, 2022, the authors identified 2,941 papers on lung cancer immunotherapy by the Web of Science and extracted their general information and the total number of citations. A bibliometric analysis was carried out to present the research landscape, demonstrate the research trends, and determine the most cited papers (top papers) as well as major journals on lung cancer immunotherapy. After that, recent research hotspots were analyzed based on the latest publications in major journals. Results These 2,941 papers were cited a total of 122,467 times. “Nivolumab vs. docetaxel in advanced non–squamous non–small–cell lung cancer” published in 2015 by Borghaei H et al. was the most cited paper (5,854 citations). Among the journals, New England Journal of Medicine was most influential. Corresponding authors represented China took part in most articles (904) and papers with corresponding authors from the USA were most cited (139.46 citations per paper). Since 2015, anti–PD–(L)1 has become the hottest research area. Conclusions This bibliometric analysis comprehensively and quantitatively presents the research trends and hotspots based on thousands of publications, and further suggests future research directions. Moreover, the results can benefit researchers to select journals and find potential collaborators. This study can help researchers get a comprehensive impression of the research landscape, historical development, and recent hotspots in lung cancer immunotherapy and provide inspiration for further research.

https://www.frontiersin.org/articles/10.3389/fimmu.2022.1032747/pdf

Global research landscape and trends of lung cancer immunotherapy: A bibliometric analysis

EP08.01-030 Nivolumab+Ipilimumab Vs Platinum-Based CT+Nivolumab In Advanced Lung Squamous-Cell Carcinoma: The Randomized SQUINT Trial

1048P Molecular predictors of immunotherapy efficacy in lung squamous-cell carcinoma (LSCC): Results from the randomized prospective SQUINT trial

http://www.annalsofoncology.org/article/S0923753422003866/pdf

VP1-2022: Pre-specified event driven analysis of Overall Survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer

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EP08.01-030 Nivolumab+Ipilimumab Vs Platinum-Based CT+Nivolumab In Advanced Lung Squamous-Cell Carcinoma: The Randomized SQUINT Trial

1048P Molecular predictors of immunotherapy efficacy in lung squamous-cell carcinoma (LSCC): Results from the randomized prospective SQUINT trial

VP1-2022: Pre-specified event driven analysis of Overall Survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer