In the evolving landscape of breast cancer treatment, triple-negative breast cancer (TNBC) continues to pose significant clinical challenges due to its aggressive nature and limited targeted therapy options. A new multicenter real-world study published in BMC Cancer sheds light on the nuanced role of carboplatin, a platinum-based chemotherapy agent, in improving treatment responses and survival outcomes in TNBC patients receiving neoadjuvant chemotherapy (NACT). Strikingly, this investigation explores the differential impact of carboplatin addition in subgroups defined by HER2 expression levels—specifically HER2-low and HER2-zero statuses—contributing valuable insights to precision oncology efforts.
TNBC is characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), leading to a distinctive clinical entity that responds poorly to hormone therapy and HER2-targeted agents. Traditionally, TNBC patients are treated with cytotoxic chemotherapy, and neoadjuvant chemotherapy aims to reduce tumor burden before surgery and improve long-term outcomes. While pCR—pathologic complete response—is a critical surrogate marker associated with improved survival, understanding factors influencing pCR rates remains crucial, especially regarding additions to standard chemotherapy regimens.
In this comprehensive study, the research team enrolled 269 patients diagnosed with locally advanced TNBC across five oncology centers. The cohort was stratified based on HER2 immunohistochemical expression into two groups: HER2-low (comprising 56.5% of the cohort) and HER2-zero (43.5%). HER2-low expression refers to HER2 scores of 1+ or 2+ with fluorescence in situ hybridization negative (FISH-), which recent research suggests may represent a biologically distinct subgroup from the classical HER2-zero TNBC with absent HER2 expression.
A crucial component of the investigation involved assessing the clinical benefit of incorporating carboplatin into standard anthracycline- and taxane-based NACT protocols across both HER2 expression subgroups. Of the participants, approximately one-quarter in each subgroup received carboplatin. The key measures evaluated included rates of pathologic complete response post-NACT, as well as disease-free survival (DFS) and overall survival (OS) metrics during follow-up periods.
The results demonstrated a compelling stratified impact of carboplatin. Firstly, the HER2-zero subgroup exhibited significantly higher overall pCR rates compared to the HER2-low group—45.2% versus 23.7%, respectively. This indicates an inherent biological responsiveness difference linked to HER2 expression status within TNBC cases. More importantly, in the HER2-zero group, carboplatin addition dramatically elevated pCR rates to 63.3%, a substantial increase over the 39.0% observed with standard NACT alone. Parallel benefits were observed in the HER2-low group, where carboplatin raised pCR rates from 19.3% to 36.8%.
Despite these encouraging improvements in pCR, the study identified important nuances indicating that certain patient subsets did not derive the same carboplatin-associated benefits. Notably, patients with Grade 1 tumors, HER2 score 2-FISH negative tumors specifically, and those with known BRCA mutations did not experience significant increases in pCR with carboplatin. These findings underscore that tumor biology and genetic background critically modulate chemosensitivity and that carboplatin is not universally efficacious across all TNBC phenotypes.
Survival analyses further reinforced the prognostic importance of achieving pCR, regardless of HER2 status or carboplatin use. Patients who reached pCR demonstrated significantly prolonged disease-free and overall survival compared to those with residual disease post-NACT. This confirms pCR as a robust surrogate endpoint linked to long-term treatment success in TNBC and validates efforts to optimize neoadjuvant regimens toward maximizing pCR.
This research holds profound clinical implications, advocating for the consideration of carboplatin as an adjunct to standard NACT backbones in TNBC patients, irrespective of HER2-zero or HER2-low classification. The findings suggest that HER2-low status should not exclude patients from receiving carboplatin, countering some earlier concepts that HER2-low TNBC might behave distinctly enough to warrant separate treatment paradigms. Instead, carboplatin’s platinum-induced DNA crosslinking efficacy appears beneficial across this heterogenous group when carefully selected.
Importantly, the authors advise judicious patient selection considering individual toxicity profiles and tumor characteristics, emphasizing that carboplatin use should be tailored rather than universally applied. The absence of benefit in certain subgroups points to the necessity for biomarker-driven precision medicine approaches that integrate genomic and histopathological data to inform treatment intensification or de-escalation strategies.
Methodologically, this multicenter real-world study expands the evidence base beyond clinical trials by capturing patient outcomes in routine oncologic practice settings. Such pragmatic data complement controlled trial findings and can better represent diverse demographics and variable clinical contexts. However, the authors acknowledge limitations including retrospective analyses and possible selection biases inherent to observational designs, which warrant further prospective validation.
Looking forward, the delineation of molecular signatures and potential predictive biomarkers may enhance the ability to forecast which TNBC patients will benefit most from carboplatin-based regimens. Integration with emerging immunotherapy strategies and novel agents targeting DNA repair pathways, such as PARP inhibitors, could further refine multimodal neoadjuvant approaches to improve cure rates.
In conclusion, this pioneering study in the nuanced domain of HER2 expression variants within TNBC demonstrates that carboplatin significantly elevates pathologic complete response rates and improves survival outcomes across HER2-zero and HER2-low patient groups. These findings recommend reconsideration of carboplatin’s role in current neoadjuvant protocols and support its selective inclusion to optimize treatment efficacy in this challenging breast cancer subtype. Future efforts should focus on mechanistic studies and personalized oncology trials to further harness carboplatin’s potential in transforming TNBC prognosis.
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**Subject of Research:** Triple-negative breast cancer; impact of carboplatin on pathologic complete response and survival based on HER2 expression status.
**Article Title:** The impact of carboplatin on pathologic complete response and survival based on HER2 low and HER2 zero status in triple negative breast cancer patients receiving neoadjuvant chemotherapy: a multicenter real-world analysis.
**Article References:**
Yıldırım, S., Başoğlu, T., Doğan, A. et al. BMC Cancer 25, 833 (2025). https://doi.org/10.1186/s12885-025-14252-3
**Image Credits:** Scienmag.com
**DOI:** https://doi.org/10.1186/s12885-025-14252-3
**Keywords:**
carboplatin treatment in triple negative breast cancer, chemotherapy response in HER2 subgroups, efficacy of carboplatin in chemotherapy, HER2 zero status in triple negative breast cancer, impact of carboplatin on survival rates, multicenter analysis of cancer treatment, neoadjuvant chemotherapy for HER2 low status, neoadjuvant therapy effectiveness in TNBC, pathologic complete response in TNBC, real-world study on breast cancer, survival outcomes in breast cancer patients, triple-negative breast cancer prognosis
