Predictive Factors of Long-Term Survival after Neoadjuvant Radiotherapy and Chemotherapy in High-Risk Breast Cancer

Jan Haussmann; Wilfried Budach; Carolin Nestle-Krämling; Sylvia Wollandt; Balint Tamaskovics; Stefanie Corradini; Edwin Bölke; David Krug; Tanja Fehm; Eugen Ruckhäberle; Werner Audretsch; Danny Jazmati; Christiane Matuschek

doi:10.3390/cancers14164031

Predictive Factors of Long-Term Survival after Neoadjuvant Radiotherapy and Chemotherapy in High-Risk Breast Cancer

Cancers (Basel). 2022 Aug 20;14(16):4031. doi: 10.3390/cancers14164031.

Affiliations

¹ Department of Radiation Oncology, Heinrich Heine University, 40225 Dusseldorf, Germany.
² Department of Gynecology and Obstetrics, Evangelisches Krankenhaus Dusseldorf, 40217 Dusseldorf, Germany.
³ Department of Senology, Sana-Kliniken Duesseldorf-Gerresheim, 40625 Dusseldorf, Germany.
⁴ Department of Radiation Oncology, University Hospital, Ludwig-Maximilians University (LMU), 80366 Munich, Germany.
⁵ Department of Radiation Oncology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
⁶ Department of Gynecology and Obstetrics, Heinrich Heine University, 40225 Dusseldorf, Germany.
⁷ Department of Senology and Breast Surgery, Breast Center at Marien Hospital Cancer Center, 40479 Dusseldorf, Germany.

Abstract

Background: Neoadjuvant radiotherapy (naRT) in addition to neoadjuvant chemotherapy (naCT) has been used for locally advanced, inoperable breast cancer or to allow breast conserving surgery (BCS). Retrospective analyses suggest that naRT + naCT might result in an improvement in pathological complete response (pCR rate and disease-free survival). pCR is a surrogate parameter for improved event-free and overall survival (OS) and allows for the adaption of the post-neoadjuvant therapy regimens. However, it is not clear whether pCR achieved with the addition of naRT has the same prognostic value.

Patients and methods: We performed a retrospective re-analysis of 356 patients (cT1-cT4/cN0-N+) treated with naRT and naCT with a long-term follow-up. Patients underwent naRT on the breast and regional lymph nodes combined with a boost to the primary tumor. Chemotherapy with different agents was given either sequentially or concomitantly to naRT. We used the Cox proportional hazard regression model to estimate the effect of pCR in our cohort in different subgroups as well as chemotherapy protocols. Clinical response markers correlating with OS were also analyzed.

Results: For patients with median follow-ups of 20 years, 10 years, 15 years, 20 years, and 25 years, OS rates were 69.7%, 60.6%, 53.1%, and 45.1%, respectively. pCR was achieved in 31.1% of patients and associated with a significant improvement in OS (HR = 0.58; CI-95%: 0.41-0.80; p = 0.001). The prognostic impact of pCR was evident across breast cancer subtypes and chemotherapy regimens. Multivariate analysis showed that age, clinical tumor and nodal stage, chemotherapy, and pCR were prognostic for OS.

Conclusion: NaCT and naRT prior to surgical resection achieve good long-term survival in high-risk breast cancer. pCR after naRT maintains its prognostic value in breast cancer subtypes and across different subgroups. pCR driven by naRT and naCT independently influences long-term survival.

Keywords: breast cancer; neoadjuvant chemotherapy; neoadjuvant radiotherapy; overall survival; pCR.

Grants and funding

This research received no external funding.