Beyond HR+: How to Apply Molecular Testing in TNBC, HER2+, and Triple Positive Breast Cancer
Breast cancer is not a single disease—and its subtypes demand tailored diagnostic and treatment approaches.
While hormone receptor-positive (HR+) breast cancer accounts for the majority of cases, clinicians managing triple negative, HER2-positive, or triple positive breast cancer face a different set of challenges, especially when it comes to identifying therapeutic targets and monitoring response.
In these patients, Northstar Select® and Northstar Response® can support timely, non-invasive insights that shape treatment planning and enable earlier intervention.
Triple Negative Breast Cancer (TNBC): Limited Targets, aggressive disease
Triple negative breast cancer (TNBC) represents ~12% of breast cancer diagnoses. It’s defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) protein expression.
Key challenges:
- Few targeted therapy options
- Aggressive biology, with early recurrence and poorer outcomes
- Standard treatments rely heavily on chemotherapy ± immunotherapy
These patients tend to have more toxic, more expensive regimens. Knowing early if treatment is working matters.
Even if targetable mutations are rare, Northstar Select may identify one early, enabling more options than toxic systemic therapy alone. By measuring tumor specific methylation, NorthstarResponse is a useful tool in TNBC—offering clarity on whether chemo or chemo+IO is working before disease progresses further.
HER2-Positive Breast Cancer: Monitoring Matters
HER2-positive disease accounts for approximately 15% of breast cancer cases. These patients typically receive anti-HER2 therapies such as trastuzumab and pertuzumab, and more recently including antibody drug conjugates (ADCs) like trastuzumab deruxtecan (T-DXd).
The testing challenge:
While HER2 status is assessed by IHC or FISH, ADC therapies often cause inflammatory changes that can mimic progression on imaging (aka pseudoprogression), confounding results about therapy response.
Sometimes a tumor looks larger on scans—but this could be a response to therapy, not progression - we call this pseudoprogression. That’s where Northstar Response can help.
Triple Positive Breast Cancer: A Hybrid Approach
Triple positive breast cancer—positive for ER, PR, and HER2 makes up roughly 10% of cases. These patients benefit from both hormone and anti-HER2 therapy.
These patients may face the same imaging ambiguity as HER2+ patients on ADC therapy and the same resistance patterns as HR+ disease—making them strong candidates for both Response and Select over time.
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Rare But Clinically Relevant Alterations
Northstar Select detects clinically actionable biomarkers across all subtypes of breast cancer, including:
- BRCA1/2 (somatic) – PARP inhibitor eligibility
- PALB2, FGFR1-3, RET fusions – Targetable with specific agents
- HER2 activating mutations – Can appear even in IHC/FISH HER2 negative patients
- MSI-high – Supports consideration of immunotherapy
While these are low prevalence, they are high impact when present—and a highly sensitive liquid biopsy such as Northstar Select offers the most reliable method to identify them.
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