Evaluation of Pathologic Complete Response as a Surrogate for Long-Term Survival Outcomes in Triple-Negative Breast Cancer

Abstract

Background: Pathologic complete response (pCR) is a common efficacy endpoint in neoadjuvant therapy trials for triple-negative breast cancer (TNBC). Previous studies have shown that pCR is strongly associated with improved long-term survival outcomes, including event-free survival (EFS) and overall survival (OS). However, the trial-level associations between treatment effect on pCR and long-term survival outcomes are not well established. This study sought to evaluate these associations by incorporating more recent clinical trials in TNBC. Methods: A literature review identified published randomized controlled trials (RCTs) of neoadjuvant therapy for TNBC that reported results for both pCR and EFS/OS. Meta-regression models were performed to evaluate the association of treatment effect on pCR and EFS/OS. Sensitivity analyses were conducted to assess the impact of divergent study designs. Results: Ten comparisons from 8 RCTs (N=2,478 patients) were identified from the literature review. The log (odds ratio) of pCR was a significant predictor of the log (hazard ratio) of EFS (P=.003), with a coefficient of determination of 0.68 (95% CI, 0.41–0.95). There was a weaker association between pCR and OS (P=.18), with a coefficient of determination of 0.24 (95% CI, 0.01–0.77). Consistent results were found in the exploratory analysis and sensitivity analyses. Conclusions: This is the first study that has shown a trial-level association between pCR and survival outcomes in TNBC. By incorporating the most up-to-date RCTs, this study showed a significant trial-level association between pCR and EFS. A positive association between pCR and OS was also recorded.

Update Breast Cancer 2021 Part 1 – Prevention and Early Stages

“…Although pathologic complete response (pCR) generally predicts good outcome after neoadjuvant chemotherapy, this effect is most pronounced in patients with HER2-positivity or TNBC 53 , 54 , 55 , 56 , 57 . In patients with HR+/HER2− tumours, the interaction is less evident, which is why understanding resistance mechanisms in the neoadjuvant setting is of particular clinical relevance.…”

“…Pathologic complete response is an excellent predictor of prognosis post neoadjuvant chemotherapy, especially in patients with TNBC or HER2+ breast cancer 53 , 54 , 55 , 56 , 57 . However, for patients without pCR and even for a few patients with pCR, there could be significant differences in prognosis.…”

“…Obwohl eine pathologische Komplettremission (pCR) generell eine gute Prognose nach einer neoadjuvanten Chemotherapie vorhersagt, ist dieser Effekt bei Patientinnen mit einem HER2-positiven oder TNBC am deutlichsten 53 , 54 , 55 , 56 , 57 . Bei Patientinnen mit HR+ HER2− Tumoren ist der Zusammenhang weniger deutlich, weswegen das Verständnis für Resistenzmechanismen in der neoadjuvanten Situation von besonderer klinischer Relevanz ist.…”

“…Die pCR ist ein hervorragender Prädiktor für die Prognose nach einer neoadjuvanten Chemotherapie, insbesondere für Patientinnen mit einem TNBC oder einem HER2+ Mammakarzinom 53 , 54 , 55 , 56 , 57 . Für Patientinnen ohne eine pCR bzw.…”

Update Breast Cancer 2021 Part 3 – Current Developments in the Treatment of Early Breast Cancer: Review and Assessment of Specialised Treatment Scenarios by an International Expert Panel

“…It is, for example, the accepted standard that if the axilla is initially negative (cN0) and a macrometastasis (ycN1) is discovered in the sentinel node (SLN), an axillary lymph node dissection (ALND) is indicated. If a micrometastasis or isolated tumour cells are detected in the SLN, the SG-EBC expert panellists agree that axillary dissection is not mandatorily indicated (Supplementary Table S1; questions [43][44][45]. Prior to NAST, a suspicious axillary lymph node should be clarified by means of a core needle biopsy (CNB) and clipped/marked.…”