Hormone Receptor Positive (HR+) Breast Cancer remains the most common subtype of breast cancer, which accounts for a large portion of the total breast cancer cases in the world. Protheragen offers a comprehensive suite of services dedicated to advancing both diagnostic and therapeutic solutions for hormone receptor-positive breast cancer.
Overview of Hormone Receptor Positive Breast Cancer
Hormone Receptor Positive (HR+) Breast Cancer is the most frequent type of breast cancer, constituting almost 70% of all cases. HR+ breast cancer tends to be less aggressive than other subtypes, like triple negative breast cancer (TNBC) and HER2-positive breast cancer. This subtype is characterized by the presence of estrogen receptor (ER) and/or progesterone receptor (PR) on the cancer cells. The therapeutic paradigm for HR + breast cancer predominantly revolves around endocrine therapy, which is a form of surgery that utilizes hormones for breast cancer therapy. Still, immune checkpoint blockade (ICB) has sparse efficacy within this subtype owing to its immunosuppressive tumor microenvironment (TME) and low tumor mutational burden (TMB).
Fig.1 Currently available endocrine therapies and targeted therapies that combine with endocrine therapies for HR-positive/HER2-negative breast cancer. (Huppert L. A.,
et al., 2023)
Pathogenesis of Hormone Receptor Positive Breast Cancer
The pathogenesis of HR+ breast cancer is multifactorial, involving a complex interplay of genetic, epigenetic, and hormonal factors. Key mechanisms include:
- Hormonal Influence: Estrogen receptors (ER) and progesterone receptors (PR) being present on cancer cells enable these hormones to aid in tumor progression.
- Genetic Mutations: The development and progression of HR+ breast cancer is often the result of mutations in the PIK3CA, TP53, and CDH1 genes and others, which have been shown to occur often in this type of cancer.
- Epigenetic Changes: The changes in DNA methylation and histone shifts can result in unusual gene expression patterns, which contribute to the progression of HR+ breast cancer.
- Immune Evasion: HR+ breast tumors frequently form an immunosuppressive TME, consisting of scant TIL infiltration and abundant PD-L1 expression.
Diagnostics Development for Hormone Receptor Positive Breast Cancer
Genomic Profiling
Genomic profiling methods, including NGS, are used to determine specific genetic mutations and alterations that can guide therapeutic options and predict outcomes of care. The Cancer Genome Atlas (TCGA) has systematically defined the breast cancer genomic landscape, identifying distinct molecular subtypes alongside their characteristic genetic changes. For instance, HR+ breast cancers frequently contain PIK3CA and TP53 mutations, which tend to affect prognosis and therapeutic response.
Single-Cell Analysis
Single-cell RNA sequencing and other single-cell analysis techniques are being implemented to understand the granular differences among immune and non-immune cells within the tumor microenvironment (TME) to further comprehend the intricate relationships between cancer cells and the immune system. One study constructed a detailed single-cell atlas of immune phenotypes within the breast tumor microenvironment, thus capturing the intricate and multifaceted aspects of TME.
Therapeutics Development for Hormone Receptor Positive Breast Cancer
- Endocrine Therapy: The primary therapeutic option for patients diagnosed with HR+ breast cancer remains endocrine therapy. Tamoxifen, aromatase inhibitors like letrozole and anastrozole, and selective estrogen receptor degraders (SERDs) are all utilized in blocking estrogen's role in driving the malignancy's growth.
- Targeted Therapies: As an example, palbociclib, ribociclib, and abemaciclib are CDK4 and 6 inhibitors, which are agents designed to modulate particular molecular pathways with the intent of improving outcomes by inhibiting progression through the cell cycle.
- Immunotherapy: Although ICB has not been particularly effective for HR+ breast cancer, other studies are looking into possible synergies with chemotherapy, targeted therapy, and other immuno-modulating agents to further augment the anti-tumoral immune activity.
Table 1. Clinical trials in HR+ breast cancer. (Goldberg J., et al., 2021)
| Trial Identifier (name) |
Therapeutics |
Number of Evaluable HR+ Samples |
Patient Population |
Phase |
Results |
| Monotherapy |
| NCT02054806 (KEYNOTE-028) |
Pembrolizumab |
25 |
Metastatic
PDL1+
Heavily pretreated |
1b |
ORR of 12% (3/25), CBR was 20% with a median duration of response of 12 months |
| NCT017772004 (JAVELIN) |
Avelumab |
72 |
Metastatic
Heavily pretreated |
1b |
ORR of 2.8% (2/72), Lack of response was irrespective of PDL1 status |
| Chemotherapy Combination |
| NCT03051659 |
Pembrolizumab
Eribulin |
44 |
Metastatic
Moderately pretreated |
II |
Addition of Pembrolizumab did not affect mPFS (4.1 vs 4.2). No trend with PDL1 status, TILs, TMB. Grade 3-4 AEs were seen in 54.6% of patients |
| NCT03044730 |
Pembrolizumab
Capecitabine (16 TNBC) |
14 (16TNBC) |
Metastatic
Endocrine resistant |
II |
Of the 29 evaluable patients, ORR was 14%, CBR was 28%, with a median PFS of 4 months. The response rates did not differ between subtypes |
| NCT01042379 (ISPY-2) |
Pembrolizumab
Paclitaxel
Doxorubicin
Cyclophosphamide |
40 |
Neoadjuvant |
II |
The addition of Pembrolizumab nearly tripled the PFS (34% vs 13%). Likelihood of success in a phase III trial prediction was 99.6% |
| Other Systemic Therapies |
| NCT01042379 (ISPY-2) |
Durvalumab
Olaparib
Paclitaxel |
52 |
Neoadjuvant BRCA+/- |
II |
Estimated pCR of 28% with a 74.5% likelihood of success in a stage III trial |
| NCT02734094 (MEDIOLA) |
Durvalumab
Olaparib (21 TNBC) |
13 (21 TNBC) |
Metastatic
Endocrine resistant |
II |
Of the 30 evaluable patients, at 12 weeks, DCR was 50% with a median PFS of 8.2 months. Survival by subtype was comparable |
| NCT02779751 (JPCE) |
Pembrolizumab
Abemaciclib |
28 |
Metastatic
Endocrine resistant |
Ib |
At 12 months, ORR was 28%, DCR was 82% with a median PFS of 8.9 months |
| Radiotherapy |
| NCT03051672 |
Pembrolizumab
Radiotherapy |
18 |
Metastatic |
II |
No objective response observed |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers a comprehensive suite of services for the development of diagnostics and therapeutics for HR+ breast cancer. We leverage our expertise in drug discovery and development to identify and validate novel therapeutic targets, develop small-molecule drugs and biologics, and conduct preclinical studies.
- Karyotype Analysis Service
- Omics Analysis Service
- Biomarker Development Service
- Artificial Intelligence Service
- Customized Diagnostics Development
- Anticancer Peptide
- Gene Therapy
- Immunotherapy
- Monoclonal Antibody
- Phytotherapy
- Small Molecule Drug
- Therapeutic Cancer Vaccine
- Spontaneous HR+ Breast Cancer Models
- Carcinogen Induced Models
- Patient-derived Xenografts (PDX) Models
- Hormone-Induced Models
- Radiation-Induced Models
Protheragen's diagnostics and therapeutics development services are characterized by our state-of-the-art technologies, rigorous scientific approach, and commitment to innovation. Our services are designed to provide comprehensive and actionable insights to support the development of effective diagnostics and therapeutics for HR+ breast cancer. If you are interested in our services, please feel free to contact us.
References
- Huppert, Laura A., et al. "Systemic therapy for hormone receptor‐positive/human epidermal growth factor receptor 2‐negative early stage and metastatic breast cancer." CA: a cancer journal for clinicians 73.5 (2023): 480-515.
- Goldberg, Jonathan, et al. "The immunology of hormone receptor positive breast cancer." Frontiers in immunology 12 (2021): 674192.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
