Abstract 144P
Background
Pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT) for early breast cancer is strongly prognostic. However, pCR is not a surrogate marker for long-term outcome at a trial level. Here, we aimed to investigate which other factors affect patient outcomes following pCR.
Methods
Patients receiving NACT for non-metastatic breast cancer, diagnosed between 2007 and 2020, in the healthcare region of Stockholm-Gotland were identified using the National Quality Register for Breast Cancer. Clinicopathological data, along with treatment and patient outcome were extracted from medical charts as well as from multiple registries. Factors affecting distant relapse-free survival (DRFS) were analyzed using a multivariable, non-proportional hazards model. Hazards over time were plotted using restricted cubic spline-based estimates.
Results
Median follow-up was 6.5 years. Of 2487 patients, 661 (26.6%) attained pCR. Rates of pCR were 45.4% in HER2+, 33.9% in triple-negative and 8.6% in luminal tumors. Patients reaching pCR had improved adjusted DRFS using inverse probability weighting. Both patients with residual disease and, to a lesser extent, with pCR had a peak in distant recurrence risk 1 year post-surgery, followed by a sharp decline in risk, which however remained elevated for non-pCR patients for more than a decade postoperatively. Among patients with pCR, age (HRadj=1.04, 95% CI 1.01-1.06), T3/T4 stage (HRadj=2.02, 95% CI 1.05-3.87) and HER2 positivity (HRadj=0.34, 95% CI 0.17-0.68) were associated with DRFS, while node positivity predicted distant recurrence during the first year post surgery (HRadj=2.84, 95% CI 1.16 – 6.94) and ER positivity predicted distant recurrence at 5-10 years (HRadj=4.30, 95% CI 1.06 – 17.49). Local relapse as first site of recurrence was more common in non-pCR patients (4.8% vs 1.8%, p=0.00047). CNS relapse was not affected by pCR status (5.1% vs 3.9%, p=0.13).
Conclusions
In this population-based study, we show that patients with pCR following NACT are a heterogeneous group regarding long-term outcomes. Baseline tumor characteristics should be considered when investigating post-neoadjuvant therapy approaches.
Legal entity responsible for the study
Region Stockholm - Karolinska University Hospital.
Funding
Swedish cancer society (Cancerfonden), The research funds at Radiumhemmet (Radiumhemmets forskningsfonder).
Disclosure
J. Bergh: Other, Fees (honoraria) to Coronis and Asklepios Cancer Research AB as an invited speaker/chair from AstraZeneca and Roche, respectively: Coronis and Asklepios Cancer Research AB.; Other, Institutional honoraria as chapter co-author for UpToDate to Asklepios Medicin HB. Co-author on a chapter on “Prognostic and Predictive factors in early, non-metastatic breast cancer”: Asklepios Medicin; Other, Institutional research grants received more than ten years ago to Karolinska Institutet and/or University Hospital for molecular marker studies/ clinical studies (we are still working with the material). No personal payments for these activities: Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche and Sanofi-Aventis; Other, Stocks in Stratipath AB. The company is involved in AI based diagnostics for breast cancer: Stratipath AB. T. Foukakis: Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Gilead Sciences; Financial Interests, Personal, Expert Testimony: Affibody; Financial Interests, Personal, Royalties, Authorship of two chapters in UpToDate: Wolters Kluwer; Financial Interests, Institutional, Invited Speaker, Clinical trial support (research grant and study drug): Pfizer, AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical trial support (research grant and study drug): Novartis. A. Matikas: Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker, International co-PI of academic trial ARIADNE (EU CT: 2022-501504-95-00): AstraZeneca, Novartis, Veracyte; Financial Interests, Institutional, Invited Speaker, Registry study: Merck; Non-Financial Interests, Advisory Role: Veracyte, Roche. All other authors have declared no conflicts of interest.