Editor’s Note: Triple-negative breast cancer (TNBC), characterized by its distinct biology and limited treatment targets, remains one of the most challenging and intensely studied subtypes of breast cancer. At the 2025 ASCO Annual Meeting, several high-impact studies opened new avenues for rethinking precision strategies in early-stage TNBC. During the 6th Annual Oncology Comprehensive Therapy Conference of the Dalian Xinghai Medical Forum, Oncology Frontier invited Professor Baoliang Guo (Second Affiliated Hospital of Harbin Medical University), Professor Li Ma (Fourth Hospital of Hebei Medical University), Professor Jing Wang and Professor Yi Fang (Cancer Hospital, Chinese Academy of Medical Sciences) to interpret key ASCO data and explore evolving approaches in early TNBC treatment.Oncology Frontier: In the context of adjuvant therapy for early-stage TNBC, the Fudan Oncology team previously demonstrated the value of adding carboplatin in the PATTERN study (PCb vs. CEF-T). However, at ASCO 2025, the NRG-BR003 study reported negative results for carboplatin addition (AC-wP ± Carbo). How do you assess the role of carboplatin in adjuvant therapy for TNBC? In your view, what type of carboplatin-containing regimen might be more reasonable or feasible?
Professor Baoliang Guo: Platinum-based agents, due to their unique mechanisms of action, continue to attract attention in TNBC treatment. The role of platinum in adjuvant chemotherapy for TNBC is a topic of ongoing debate. The two studies we’re discussing today employed different strategies for incorporating platinum, and each must be evaluated on its own clinical merits.
The PATTERN study, led by Professor Zhimin Shao of Fudan University Shanghai Cancer Center and published in JAMA Oncology in 2021, included operable TNBC patients—mostly early-stage, with 74% node-negative. The trial showed that the experimental PCb regimen (paclitaxel + carboplatin) significantly improved disease-free survival compared to the control CEF-T regimen (cyclophosphamide, epirubicin, 5-fluorouracil followed by docetaxel), with a 5-year DFS of 86.5% vs. 80.3% (HR 0.65, P = 0.03). The strength of this study lies in its relevance to Chinese populations. However, its limitations include a relatively low-risk patient cohort and the use of CEF-T as a comparator, which is no longer considered a mainstream regimen. Notably, exploratory subgroup analyses suggested that patients with gBRCA1/2 mutations or HRD positivity derived greater benefit from the PCb regimen.
In contrast, the phase III NRG-BR003 study, presented at ASCO 2025, examined the addition of carboplatin to a current standard-of-care backbone—dose-dense anthracycline and taxane-based chemotherapy (AC-wP). Unfortunately, the study did not meet its primary endpoint. In high-risk TNBC patients (both node-positive and high-risk node-negative), adding carboplatin to AC-wP did not significantly improve invasive disease-free survival (5-year IDFS: 82.7% vs. 77.8%; HR 0.78; P = 0.18). While there were signals of benefit in certain subgroups, such as pN2 (HR 0.52) and BRCA-mutated patients (HR 0.388), these trends require validation in larger cohorts. Additionally, the AC-wP + Carbo arm was associated with significantly increased toxicity. Possible explanations for the negative outcome include:
- The high-risk nature of the enrolled population, potentially diminishing the additive value of platinum
- Increased toxicity from the dose-dense backbone limiting full-dose carboplatin administration
- Lack of biomarker-based patient selection, leading to population heterogeneity
Given current evidence, platinum-based regimens may be considered for Chinese patients who meet PATTERN study criteria—particularly those with BRCA mutations, HRD positivity, or those needing to avoid anthracycline-related toxicity. However, routine use of platinum with a dose-dense standard regimen is not currently supported and should not be recommended across the board. For high-risk subgroups such as pN2 or BRCA-mutated patients, individualized consideration is warranted.
Together, these two studies offer valuable insights for clinical decision-making, but precision treatment for early-stage TNBC still requires more high-quality, evidence-based validation.
Oncology Frontier: Patients with HRD or BRCA mutations are known to respond better to PARP inhibitors (PARPi) and platinum-based chemotherapy. However, the ABCSG 45 study presented at ASCO showed that combining PARPi with carboplatin as neoadjuvant therapy in this population did not produce a synergistic effect. How do you interpret these findings, and what implications might they have for clinical practice?
Professor Li Ma: The results of the phase II ABCSG 45 trial were indeed unexpected. The combination of carboplatin and PARP inhibitors did not demonstrate the anticipated synergistic efficacy. This study enrolled patients with early-stage TNBC who tested positive for homologous recombination deficiency (HRD). Participants received either standard chemotherapy (TAC: docetaxel, doxorubicin, and cyclophosphamide) or a neoadjuvant regimen of carboplatin plus a PARPi.
In BRCA-mutated patients, the carboplatin + PARPi group showed numerically higher rates of RCB 0/I (77.3% vs. 65.0%) and pathologic complete response (pCR) (77.3% vs. 65.0%) compared to the TAC group. However, in the overall cohort and in BRCA wild-type patients, both the RCB 0/I and pCR rates were actually lower in the carboplatin + PARPi group. Moreover, this group experienced higher rates of hematologic toxicity.
These findings highlight the inherent complexity of combining targeted therapies. While both PARP inhibitors and platinum agents have demonstrated strong efficacy as monotherapies in HRD-positive and BRCA-mutated populations, their combination does not necessarily guarantee an additive or synergistic effect. Factors such as tumor heterogeneity, distinct resistance mechanisms, and differences in pharmacokinetics may influence treatment outcomes. Additionally, neoadjuvant efficacy can be affected by tumor burden at diagnosis, patient fitness, and other clinical variables.
In current clinical practice, and in line with existing evidence and guidelines, we typically recommend that PARP inhibitors and platinum agents be used separately. If combination therapy is considered, it should be limited to carefully selected patients based on comprehensive evaluation—including tumor biology, prior treatment history, and performance status.
It’s also important to note that BRCA wild-type patients in the ABCSG 45 study had notably poorer outcomes with the combination regimen, underscoring the need for more refined biomarkers to predict treatment response and guide therapeutic decision-making in early TNBC.
Oncology Frontier: The NeoSTAR study presented at ASCO introduced not only a TROP2-targeting ADC into the neoadjuvant setting but also employed an adaptive “response-guided escalation/de-escalation” treatment strategy. How do you evaluate this innovative approach?
Professor Jing Wang: The NeoSTAR study stands out for two key innovations. First, it is the first clinical trial to introduce sacituzumab govitecan (SG)—a TROP2-directed antibody–drug conjugate—into the neoadjuvant setting as a single-agent therapy for TNBC. Second, the study adopted a novel, response-guided treatment approach often referred to as “therapeutic escalation and de-escalation.” This dynamic strategy allows clinicians to tailor treatment intensity based on early response.
The results are promising: SG monotherapy led to a pathological complete response (pCR) rate of approximately 30%, which is quite significant for a single-agent neoadjuvant treatment—especially considering its favorable safety profile compared to standard chemotherapy. This raises a critical question in clinical practice: for a subset of sensitive patients, can we achieve effective disease control while reducing treatment burden?
The response-adapted strategy used in NeoSTAR challenges the conventional one-size-fits-all approach. Patients showing strong responses to initial SG treatment were able to proceed directly to surgery, while those with residual disease received additional chemotherapy to intensify treatment. This embodies the core principle of precision oncology—individualizing therapy based on real-time biological response.
The clinical value of this approach lies in two aspects:
- Avoiding overtreatment for patients who are highly responsive, thereby minimizing unnecessary toxicity.
- Preserving treatment intensification for patients with suboptimal response, ensuring adequate disease control.
It is important to note that these findings are from a phase II study, and the long-term outcomes and safety data will need to be confirmed in future phase III trials. Nevertheless, the NeoSTAR trial offers a fresh perspective for neoadjuvant therapy in TNBC.
In clinical settings, we are often asked by patients and families whether every prescribed cycle of chemotherapy is absolutely necessary. The NeoSTAR study represents a forward-thinking attempt to build a more scientific and individualized framework for determining treatment intensity—one that balances efficacy with quality of life.
Oncology Frontier: With the emergence of new drug options and adaptive strategies—such as response-guided “escalation/de-escalation” models—TNBC (neo)adjuvant treatment is becoming increasingly complex. Factors like PD-L1 expression, BRCA/HRD status, and expression of ADC targets (e.g., HER2, TROP2) are now under close evaluation. As highlighted in the discussions of Professors Guo, Ma, and Wang, the ASCO 2025 presentations of NRG-BR003, ABCSG 45, and NeoSTAR offered valuable insights for early TNBC treatment. How do you interpret the impact of these studies on clinical practice?
Professor Yi Fang: In HER2-positive breast cancer, treatment strategies have become relatively well established. For example, at this year’s ASCO Annual Meeting, Professor Kun Wang presented results from the neoCARHP study, which showed that a non-carboplatin THP regimen achieved a pCR rate non-inferior to that of the carboplatin-containing TCbHP regimen, with lower toxicity. This provides compelling evidence for refining neoadjuvant therapy in HER2-positive early breast cancer. In contrast, the treatment of TNBC remains fraught with clinical uncertainties. Although the introduction of PD-1 inhibitors, BRCA mutations, and HRD as biomarkers has opened new therapeutic avenues, we have yet to see transformative breakthroughs in overall outcomes.
The three studies presented at ASCO this year have collectively deepened our understanding of TNBC treatment strategies:
- NRG-BR003, while failing to meet its primary endpoint, revealed potential benefits in specific subgroups—namely pN2 and BRCA-mutated patients. These findings suggest that platinum-based regimens may still be considered in selected high-risk patients, although clinicians must carefully balance efficacy with the increased toxicity risk.
- ABCSG 45 serves as an important cautionary tale: even rational, biologically informed combination therapies—such as PARP inhibitors with carboplatin—require rigorous clinical validation. The safety concerns and suboptimal outcomes in BRCA wild-type patients highlight the need for prudence, especially when introducing novel combinations in the neoadjuvant setting. Clinical decisions should remain rooted in robust evidence, avoiding premature adoption of unproven regimens.
- NeoSTAR demonstrates true innovation through its integration of a novel ADC (sacituzumab govitecan) with a response-guided escalation/de-escalation model. While the safety profile of SG is favorable and the pCR rate is promising (~30%), these results must be interpreted in context. Existing data show that conventional chemotherapy plus PD-1 inhibitors already yield pCR rates above 50%. Although SG-based regimens may offer comparable efficacy with lower toxicity, phase III trials are essential before changing practice. We must welcome innovation—but not at the expense of well-established standards of care.
In summary, while novel strategies continue to emerge, chemotherapy—alone or in combination with PD-(L)1 immunotherapy—remains the cornerstone of neoadjuvant treatment for TNBC. These studies encourage us to refine patient selection, explore new agents, and individualize therapy, all while upholding the principles of evidence-based medicine.
Professor Baoliang Guo Director, Department of Breast Surgery II The Second Affiliated Hospital of Harbin Medical University
Professor Li Ma Chief Physician, Professor, Doctoral Supervisor Director, Breast Center Inpatient Department The Fourth Hospital of Hebei Medical University
Professor Jing Wang MD, PhD, Chief Physician, Professor Doctoral and Postdoctoral Supervisor Director, Department of Breast Surgery Cancer Hospital, Chinese Academy of Medical Sciences
Professor Yi Fang Chief Physician, Doctoral Supervisor National Cancer Center / Cancer Hospital, Chinese Academy of Medical Sciences
