Systemic treatment for breast cancer has undergone rapid change since 2020, driven by the broader clinical application of targeted therapies, antibody–drug conjugates (ADCs), and immunotherapy across established biologic subtypes. These therapeutic classes have expanded indications in both metastatic and early-stage disease and have affected care pathways at multiple points in the patient journey. The evolving landscape has prompted reassessment of sequencing and integration of new agents into standard regimens.
A major shift in systemic management is the routine incorporation of tumor molecular profiling and germline genetic testing to inform treatment selection. These diagnostic approaches enable biomarker-guided strategies that match patients with targeted agents based on tumor biology or inherited risk. The review emphasizes that personalized treatment decisions increasingly rely on molecular and germline data, which guide selection of pathway-directed drugs, hormone modulators, and other novel agents.
In hormone-receptor–positive, HER2‑negative breast cancer, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors remain a foundational component of systemic therapy. These agents continue to be central in front-line endocrine-based regimens.
For patients who develop endocrine resistance, several new classes of agents have meaningfully altered management options. Inhibitors that target the phosphatidylinositol 3‑kinase (PI3K) pathway, oral selective estrogen‑receptor degraders (SERDs), and antibody–drug conjugates are now part of the post‑endocrine resistance armamentarium. The review notes that these therapies have reshaped decision-making for patients whose tumors no longer respond to standard endocrine interventions.
Advances in HER2‑positive breast cancer have been dominated by the development and wider use of antibody–drug conjugates. The review calls out trastuzumab deruxtecan in particular as an ADC that has improved clinical outcomes and is being used earlier in the treatment sequence. As ADCs move into earlier lines of therapy, traditional paradigms for HER2‑directed management are being reconfigured, prompting reassessment of when and how to use older HER2‑targeted agents versus newer conjugates.
In triple‑negative breast cancer, the review highlights that immune checkpoint inhibitors have produced outcome improvements in both metastatic and early‑stage disease. Immunotherapy has therefore become an important component of systemic options for patients with triple‑negative biology, expanding the therapeutic toolkit beyond conventional cytotoxic chemotherapy.
Across breast cancer subtypes, contemporary curative‑intent strategies increasingly emphasize risk‑adapted escalation and de‑escalation. This approach aims to tailor the intensity of systemic therapy to individual patient risk, potentially reducing overtreatment for low‑risk patients while escalating therapy for those at higher risk of recurrence. The review frames this trend as a central principle guiding integration of new agents into early‑stage care.
The review identifies several emerging diagnostic and monitoring tools that have the potential to refine systemic treatment decisions. Analysis of circulating tumor DNA (ctDNA) is discussed as an example of a technology that may help in treatment selection, detection of minimal residual disease, and surveillance, although the review emphasizes the need for further integration and validation of such tools in clinical practice.
Despite therapeutic advances, the review highlights multiple ongoing challenges. Optimal sequencing of the expanding range of active agents remains unsettled across subtypes. There is a continuing need to identify and validate predictive biomarkers that reliably select patients most likely to benefit from particular therapies. Practical and policy issues are also emphasized: many newer drugs and ADCs are high cost, and the review calls attention to the importance of ensuring equitable access to these therapies.
The review provides a high‑level synthesis of how targeted therapies, ADCs, immunotherapy, and improved molecular diagnostics have changed systemic breast cancer care since 2020, while underscoring unanswered questions about sequencing, biomarker development, integration of emerging assays such as ctDNA, and health‑system challenges related to cost and access. Specific trial names, numerical outcome data, and detailed recommendations were not reported in the abstract and are not reproduced here.