Approximately 15-20% of breast cancer cases are HER2-positive (HER2+). They are characterized by an overexpression of the HER2 protein, which plays an important role in the growth and progression of the tumor. But, at the same time, it presents a unique therapeutic opportunity, as targeted treatments such as trastuzumab and pertuzumab have been shown to be more effective and have fewer side effects than traditional chemotherapy in patients with HER2+ breast cancer. Furthermore, combining biologic anti-HER2 agents with chemotherapy has proven highly effective in treating patients with HER2+ breast cancer, resulting in significant clinical improvement and better patient outcomes.
However, not all patients respond to these treatments in the same way. By using a combination of biomarkers, oncologists could more accurately predict which patients are likely to respond to these therapies and tailor treatment plans accordingly. During the last ESMO Breast Cancer in Berlin last spring, our CSO, Prof. Aleix Prat MD, Ph.D., highlighted that:
- Clinical variables and features from tumor cells and the immune microenvironment can predict the pathological complete response (pCR) and survival outcome and should help tailor therapy.
- A positive response to treatment does not always directly translate to improved survival. It could be related to the different biological mechanisms that drive the pCR response and the survival outcome.
- Immune signatures (especially B-cell related) may provide more accurate or helpful information than other biomarkers, such as Tumor-infiltrating Lymphocytes (TILs).
The future of treating patients with HER2+ breast cancer lies in optimizing treatment personalization. If you are interested, please watch our HER2DX® TALKS to get more robust scientific data that validates the first genomic tool for patients with HER2+ breast cancer and how it can be key to clinical decision-making.
Trastuzumab has significantly impacted the outcome of patients with HER2+ breast cancer, transforming it from a highly aggressive subtype to a much better prognosis. The current standard of care for patients with early-stage HER2+ breast cancer is to receive chemotherapy in combination with trastuzumab for one year.
However, the treatment duration for trastuzumab was not based on robust preclinical or clinical data. The current standard treatment can be costly, lengthy, and occasionally associated with cardiac adverse events. In recent years, studies have investigated alternative treatment options such as reducing the treatment duration and toxicity (de-escalation) or increasing the effectiveness of treatment through dual HER2 inhibition or extended treatment duration (escalation).
Oncologists use a variety of factors to determine whether it is safe to escalate or de-escalate treatment for a patient with breast cancer: specific characteristics of the patient's tumor, overall health, medical history, etc. They also consider the patient's preferences, treatment goals, age, comorbidities, and life expectancy.
Especially for de-escalation, predictors of pCR and distant events are needed to identify candidates better, and HER2DX® meets these two different endpoints, as it is indicated either as:
- A prognostic indicator for disease-free survival in pre- and post‐menopausal women or men with HER2+ early-stage I-III breast cancer, regardless of hormone receptor status, when used in conjunction with other clinical factors.
-A predictive indicator of pCR following neoadjuvant anti-HER2-based therapy.
It is important to note that de-escalation of treatment should be done under close monitoring to evaluate the patient's response to the new treatment plan and adjust as needed.
Scientific validation is crucial for any new tool in the field of oncology, as it ensures that it works. This process involves conducting research and clinical trials to gather evidence to support its use.
HER2DX® has been validated in more than 2,000 patients, and different clinical studies have shown it to accurately identify patients likely to respond to treatment and improve outcomes. APT and ATEMPT trials demonstrated high efficacy of a de-escalation strategy based on paclitaxel and trastuzumab, or trastuzumab emtansine, an anti-HER2 antibody drug-conjugate. On the other hand, DAPHNe and GOM studies shed light on HER2DX® pCR predictability. Notably, in DAPHNe, the pCR rate in patients with HER2+ breast cancer treated with neoadjuvant THP with a HER2DX® high pCR likelihood was 93%. These results, obtained in collaboration with Dana-Farber Cancer Institute, were presented at the San Antonio Breast Cancer Symposium last December, and will be published soon.
Nevertheless, it takes more than scientific validation for a new tool to be genuinely revolutionary: experts' opinions on implementation in clinical practice are essential.
Recently, independently conducted surveys of breast cancer oncologists about the clinical impact of HER2DX® showed that it may be helpful in therapeutic management, with 66% thinking that it can already help make treatment decisions in selected patients, and it gives confidence in the final treatment decision, as reported in 76% of cases. Future prospective studies will contribute to defining the role of the HER2DX® risk score and pCR score in routine clinical practice.
HER2DX® is a 27-gene plus clinical feature-based classifier that provides accurate estimates of the risk of recurrence and the probability of achieving a pCR in early-stage HER2+ breast cancer.
To order a HER2DX® test, follow these simple steps:
1. The physician requests HER2DX® (contact Reveal Genomics at: HER2DX@reveal-genomics.com and complete the test requisition form).
2. A pre-treated baseline tumor formalin-fixed paraffin-embedded (FFPE) sample is sent to the central lab (no new biopsy is required).
3. RNA extraction and data analysis are performed (using algorithms specifically designed to provide independent prognostic and predictive information).
4. A HER2DX® report is generated (providing information about the relapse risk score, pCR likelihood score, and ERBB2 mRNA expression levels).
5. HER2DX® results guide physicians and patients in their decision-making process.
Now, patients with early-stage HER2+ breast cancer are only five steps away from multiple benefits.
References
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· Prat A, Guarneri V, Paré L, Griguolo G, Pascual T, Dieci MV, Chic N, González-Farré B, Frassoldati A, Sanfeliu E, Cejalvo JM, Muñoz M, Bisagni G, Brasó-Maristany F, Urso L, Vidal M, Brandes AA, Adamo B, Musolino A, Miglietta F, Conte B, Oliveira M, Saura C, Pernas S, Alarcón J, Llombart-Cussac A, Cortés J, Manso L, López R, Ciruelos E, Schettini F, Villagrasa P, Carey LA, Perou CM, Piacentini F, D'Amico R, Tagliafico E, Parker JS, Conte P. A multivariable prognostic score to guide systemic therapy in early-stage HER2-positive breast cancer: a retrospective study with an external evaluation. Lancet Oncol. 2020 Nov;21(11):1455-1464.
· Prat A, Guarneri V, Pascual T, Brasó-Maristany F, Sanfeliu E, Paré L, Schettini F, Martínez D, Jares P, Griguolo G, Dieci MV, Cortés J, Llombart-Cussac A, Conte B, Marín-Aguilera M, Chic N, Puig-Butillé JA, Martínez A, Galván P, Tsai YH, González-Farré B, Mira A, Vivancos A, Villagrasa P, Parker JS, Conte P, Perou CM. Development and validation of the new HER2DX assay for predicting pathological response and survival outcome in early-stage HER2-positive breast cancer. EBioMedicine. 2022 Jan;75:103801.