Breast cancer remains a leading cause of morbidity and mortality among women worldwide. Hormone receptor-positive (HR+) breast cancer, which expresses estrogen or progesterone receptors, constitutes the most prevalent subtype of breast cancer. Its treatment paradigm traditionally includes hormonal therapy and/or chemotherapy. The recent years have seen growing interest in the immunological aspects of HR+ breast cancer—the immune microenvironment and its potential impacts on treatment outcomes. A pivotal study published in the “Clinical Cancer Research,” an official journal of the American Association for Cancer Research, with DOI: 10.1158/1078-0432.CCR-19-0173, delves into the immune milieu of HR+ breast cancers before and after preoperative chemotherapy and offers a wealth of insights into possible prognostic markers and therapeutic targets.
Introduction to the Immune Microenvironment in HR+ Breast Cancer
Breast cancer has long been perceived as a less immunogenic tumor compared to melanomas or lung cancers. However, the immune microenvironment comprising various cells plays a critical role in the progression and therapeutic responsiveness of cancers, including HR+ breast cancer. Tumors are infiltrated by a multitude of immune cells such as T lymphocytes, macrophages, natural killer cells, and dendritic cells, whose interactions create a complex network influencing tumorigenesis, tumor progression, and response to treatment.
Recently, the focus on immunotherapy, particularly the use of checkpoint inhibitors, has surged in oncology research. Exploring the relationship between breast tumors and the immune system can unravel new opportunities for enhancing the efficacy of existing treatments and developing novel therapeutic strategies.
Transformation of the Immune Microenvironment Post-Chemotherapy
The study in question, led by Sara M. Tolaney et al., aimed at deciphering the changes in immune microenvironment of HR+ breast cancer patients after preoperative chemotherapy. It involved a detailed scrutiny of tumor tissues collected from two cohorts—before and after treatment. The findings shed light on the immune evasion mechanisms adopted by tumor cells and their implications for patient outcomes.
Therapeutic Implications & Responses
The research provides a tantalizing look at the potential immune profiles that might predict responsiveness to chemotherapy. For instance, the density of CD8-positive T cells, known for their cytotoxic ability to kill cancer cells, was substantially higher after chemotherapy. This suggests that the recruitment or encroachment of these immune cells could possibly be attributed to the cytotoxic effects of chemotherapy that may expose tumor antigens, thus spurring an immune reaction.
Moreover, a key highlight of the research findings showed an association between the expression of programmed death-ligand 1 (PD-L1) on tumor cells and the influx of immune cells. PD-L1, a protein that cancer cells use to protect themselves from the immune system, becomes a beacon for immune checkpoint inhibitors. Drugs blocking the PD-L1 pathway can render cancer cells vulnerable to the immune system’s attack, a foundation upon which many immunotherapies are currently built.
Clinical Outcomes & Prognosis
A particularly interesting observation was the variance in tumor-infiltrating lymphocytes (TILs) before and after chemotherapy. TILs are considered a robust marker for immunogenicity and have been correlated with survival rates in various cancers. In HR+ breast cancer, the post-therapy increase in TILs corresponded with improved pathological complete response (pCR), indicating their potential as a prognostic marker for treatment response.
The study also underlines the importance of immune composition within tumors. The findings align with previous research suggesting that not only the presence but also the types of immune cells infiltrating breast tumors can significantly impact prognostic outcomes. For example, a higher ratio of M1 macrophages, which exhibit antitumor activity, to M2 macrophages, that promote tumor progression, is desirable for a better prognosis.
Future Directions and Ongoing Investigations
This research represents an initial foray into the complex interplay between chemotherapy and the immune microenvironment in HR+ breast cancer. It paves the way for further investigations into treatments that can modulate the immune milieu for therapeutic gain. Clinical trials testing the synergy between chemotherapy and immunotherapy such as pembrolizumab for HR+/HER2- breast cancer are ongoing, thus expanding the horizons of personalized medicine in oncology.
References
1. Waks AG, et al. The Immune Microenvironment in Hormone Receptor-Positive Breast Cancer Before and After Preoperative Chemotherapy. Clin Cancer Res. 2019;25(15):4644-4655. doi: 10.1158/1078-0432.CCR-19-0173.
2. Howlader N, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5). doi: 10.1093/jnci/dju055.
3. Muenst S, et al. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 2014;146(1):15–24. doi: 10.1007/s10549-014-2988-5.
4. Rugo HS, et al. Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Clin Cancer Res. 2018;24(12):2804–11. doi: 10.1158/1078-0432.Ccr-17-3452.
5. Salgado R, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259–71. doi: 10.1093/annonc/mdu450.
Keywords
1. Hormone receptor-positive breast cancer
2. Immune microenvironment
3. Preoperative chemotherapy
4. Tumor-infiltrating lymphocytes
5. Programmed death-ligand 1 (PD-L1)
Concluding Remarks
In sum, the study led by Tolaney et al. enriches our understanding of the immune microenvironment in HR+ breast cancer and its transformation resulting from preoperative chemotherapy. It highlights the potential biomarkers for predicting response to treatment and underscores the need for integrated therapies that combine the powers of immune modulation and conventional chemotherapy. The high caliber of this research accentuates the thrust toward precision medicine in oncology and kindles hope for improved prognostication and individualized patient care in HR+ breast cancer.