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The Role of Aromatase Inhibitors in Breast Cancer Treatment
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The Role of Aromatase Inhibitors in Breast Cancer Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 1 September 2025 | Viewed by 4155

Special Issue Editor

Dr. Chandra Bhushan Mishra

E-Mail Website
Guest Editor
Department of Pharmacology & Chemical Biology, Baylor College of Medicine, Baylor Plaza, Houston, TX 77030, USA
Interests: breast cancer; vitro anticancer; enzyme; novel inhibitors

Special Issue Information

Dear Colleagues,

Aromatase inhibitors play a crucial role in breast cancer treatment by blocking the enzyme aromatase, which is responsible for estrogen production. Estrogen fuels the growth of hormone receptor-positive breast cancers, and these inhibitors help reduce estrogen levels, inhibiting cancer cell proliferation. Often used in postmenopausal women, aromatase inhibitors are a key component of hormone therapy, complementing other treatments to improve outcomes and reduce the risk of cancer recurrence.

Dr. Chandra Bhushan Mishra
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • aromatase inhibitors
  • breast cancer
  • enzyme aromatase
  • estrogen

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Published Papers (3 papers)

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Research

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14 pages, 2244 KB  
Article
CDK4/6 Inhibitors-Induced Macrocytosis Is Not Associated with Hemolysis and Does Not Impact Hemoglobin Homeostasis
by Tiago Barroso, Leila Costa, Lisa Gonçalves, Vanessa Patel, João Araújo, Inês Pinho, Carolina Monteiro, Miguel Esperança-Martins, Catarina Abreu, Rita Teixeira de Sousa, Helena Pais, Gonçalo Nogueira-Costa, Sofia Torres, Leonor Abreu Ribeiro and Luís Marques da Costa
Cancers 2025, 17(9), 1567; https://doi.org/10.3390/cancers17091567 - 5 May 2025
Viewed by 856
Abstract
Background: CDK 4/6 inhibitors (CDK4/6is) are the first-line treatment for metastatic luminal-like breast cancer (BC). These drugs induce macrocytosis without anemia in most patients. The mechanism for the red blood cell (RBC) changes is unknown. In vitro and animal studies show that RBCs [...] Read more.
Background: CDK 4/6 inhibitors (CDK4/6is) are the first-line treatment for metastatic luminal-like breast cancer (BC). These drugs induce macrocytosis without anemia in most patients. The mechanism for the red blood cell (RBC) changes is unknown. In vitro and animal studies show that RBCs from CDK6-knockout mice have increased membrane fragility, but the clinical impact of CDK4/6is on human RBC lifespan is not known. We sought to determine the impact of CDK4/6is on RBC lifespan and detect changes in the regulation of hemoglobin production. Using the mean corpuscular volume (MCV) measurements at several time points, we can study the evolution of MCV, mean corpuscular hemoglobin concentration (MCHC), and RBC count over time. From this, one can estimate the RBC lifespan under CDK4/6is. Methods: We performed a unicentric retrospective study. Based on published models of RBC population dynamics, we have coded a biologically inspired model which allowed us to extract values for biological parameters, including the RBC lifespan. Results: A total of 122 patients were identified, and 1959 laboratory measurements were analyzed. After the pre-treatment RBCs were replaced, the mean MCV increased by 12.6 femtoliter (fL) (95% Bayesian credible interval [CdI] 13–14), the MCHC increased slightly by 0.69 g/dL (95% CdI 0.42–0.96), and the RBC count decreased by 0.77 × 109/L (95% CdI 0.42 × 109/L–0.96 × 109/L). The net result was a 0.64 g/dL (95% CdI 0.48–0.80) rise in hemoglobin. The mean total RBC lifetime was 118 days (95% CdI 114–122), similar to the value measured in healthy persons. Discussion and Conclusions: These findings suggest that, despite changes in RBC volume, CDK4/6is do not predispose patients to RBC destruction and do not impair regulation of hemoglobin homeostasis. We show that CDK4/6is do not decrease the RBC lifespan in pre-treatment erythrocytes. Unfortunately, this method cannot determine the lifespan of post-treatment RBCs, but further research could help answer this question. Full article
(This article belongs to the Special Issue The Role of Aromatase Inhibitors in Breast Cancer Treatment)
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13 pages, 1661 KB  
Article
Subtype-Specific Survival of Young Women with Breast Cancer and Its Interaction with the Germline BRCA Status
by Anna Maria Hage, Pimrapat Gebert, Jens-Uwe Blohmer, Elham Hedayati, Dorothee Speiser and Maria Margarete Karsten
Cancers 2024, 16(4), 738; https://doi.org/10.3390/cancers16040738 - 10 Feb 2024
Cited by 1 | Viewed by 2090
Abstract
Data are scarce on the role of pathogenic germline variants in BRCA1 and BRCA2 (gBRCAm) in subtype-specific survival in young women who develop breast cancer under the age of 40. This retrospective, real-world cohort study assessed the distant disease-free survival (DDFS) and overall [...] Read more.
Data are scarce on the role of pathogenic germline variants in BRCA1 and BRCA2 (gBRCAm) in subtype-specific survival in young women who develop breast cancer under the age of 40. This retrospective, real-world cohort study assessed the distant disease-free survival (DDFS) and overall survival (OS) of young women diagnosed with breast cancer between 2008 and 2019 while taking into consideration the interaction of clinical subtypes and the gBRCA status. Among 473 women, HR+/Her2− was the most common subtype (49.0%), followed by TNBC (31.3%), HR+/Her2+ (13.7%), and Her2+/HR− (5.9%). The gBRCA status was known for 319 cases (gBRCAwt (wild-type – without pathogenic variants in BRCA1 or BRCA2): 204, gBRCA1m: 83, gBRCA2m: 31, 1 patient with both). The distribution of clinical subtypes varied depending on the gBRCA status (p < 0.001). In survival analysis with a median follow-up of 43 months, the unadjusted DDFS and OS were worse for gBRCAwt TNBC compared to both HR+ subtypes, but not for gBRCAm TNBC patients. T-stage, nodal involvement, and the gBRCA status were identified as significant for survival in TNBC. In TNBC, gBRCAm was associated with better DDFS and OS than gBRCAwt (5-year DDFS 81.4% vs. 54.3%, p = 0.012 and 5-year OS 96.7% vs. 62.7%, p < 0.001). In contrast, in HR+/Her2− patients, gBRCAm patients showed a tendency for worse survival, though not statistically significant. Subtype-specific survival in young women with breast cancer needs to be evaluated in interaction with the gBRCA status. For TNBC, gBRCAm is of favorable prognostic value for overall survival, while patients with gBRCAwt TNBC need to be considered to have the highest risk for adverse survival outcomes. Full article
(This article belongs to the Special Issue The Role of Aromatase Inhibitors in Breast Cancer Treatment)
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Review

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31 pages, 1201 KB  
Review
Aromatase Inhibitors as Adjuvant Therapy in Early Breast Cancer: Insights into Toxicities and Their Management
by Simone Nardin, Beatrice Ruffilli, Tommaso Lupo Landolfo, Giulia Isingrini, Ida Taglialatela, Andrea Delbarba, Francesca D’Avanzo, Valentina Rossi, Eduardo Celentano, Benedetta Conte, Matteo Nardin and Alessandra Gennari
Cancers 2025, 17(17), 2726; https://doi.org/10.3390/cancers17172726 - 22 Aug 2025
Viewed by 428
Abstract
Aromatase inhibitors (AIs), with or without gonadotropin-releasing hormone analogs, are the cornerstone of adjuvant endocrine therapy for women with hormone receptor-positive early-stage breast cancer, offering significant reductions in recurrence risk and improving long-term survival. Their use is frequently accompanied by treatment-related toxicities that [...] Read more.
Aromatase inhibitors (AIs), with or without gonadotropin-releasing hormone analogs, are the cornerstone of adjuvant endocrine therapy for women with hormone receptor-positive early-stage breast cancer, offering significant reductions in recurrence risk and improving long-term survival. Their use is frequently accompanied by treatment-related toxicities that can adversely affect patients’ quality of life (QoL) and adherence to therapy. Commonly reported side effects include vasomotor symptoms, such as hot flashes; musculoskeletal disorders, such as arthralgia and myalgia; mood disorders; and genitourinary discomfort, such as vaginal dryness and dyspareunia. Additionally, AIs are associated with a heightened risk of bone loss, leading to osteoporosis and fractures, and may have implications for cardiovascular health. Effective management of these adverse events is pivotal in maintaining treatment adherence and preserving QoL. Evidence-based strategies to address these toxicities include pharmacological interventions, such as analgesics for joint pain, bisphosphonates or denosumab for bone health, and hormonal or non-hormonal approaches for vasomotor and genitourinary symptoms. Non-pharmacological measures, including physical activity, dietary adjustments, and complementary therapies, can also help mitigate symptoms. This review examines the broad spectrum of AI-associated toxicities, discusses their clinical implications, and provides an overview of evidence-based management strategies. These insights aim to support clinicians in optimizing patient care while minimizing the toxicities of therapy. Full article
(This article belongs to the Special Issue The Role of Aromatase Inhibitors in Breast Cancer Treatment)
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