ABSTRACT
Background:
Understanding the
survival outcomes associated with
breast-conserving
therapy (BCT) and
mastectomy after preoperative systemic
therapy (PST) enables clinicians to provide more personalized
treatment recommendations. However, lack of firm
survival benefit data limits the
breast surgery choices of
human epidermal growth factor receptor 2 (HER2)-positive
breast cancer patients who receive PST. We sought to determine whether BCT or
mastectomy after PST for early operable HER2-positive
breast cancer is associated with better long-term
survival outcomes and determine the degree to which PST response
affects this
association.
Methods:
In this observational
cohort study, we compared the long-term
survival outcomes of BCT and
mastectomy after PST for HER2-positive
breast cancer and evaluated the impact of PST response on the relationship between
breast surgery performed and
survival outcomes. Our cohort included 625
patients with early operable HER2-positive
breast cancer who received PST followed by BCT or
mastectomy between January 1998 and October 2009. These
patients also received standard postoperative
radiation,
trastuzumab, and endocrine
therapy as indicated clinically. We used
propensity score matching to assemble
mastectomy and BCT cohorts with
similar baseline characteristics and used Kaplan-Meier plots and Cox proportional
hazards regression to detect
associations between
surgery types and outcomes. Furthermore, in this study, we analyzed the original data of 625
patients using the inverse
probability of
treatment weighting (IPTW)
method to enhance the reliability of the comparison between the
mastectomy and BCT cohorts by addressing potential
confounding variables.
Findings:
Propensity score matching yielded cohorts of 221
patients who received BCT and 221
patients who underwent
mastectomy. At the median follow-up
time of 9.9 years, compared with BCT,
mastectomy was associated with worse overall
survival (
hazard ratio, 1.66; 95%
confidence interval [CI] 1.08-2.57; P = 0.02). In
patients who had axillary
lymph node pathological complete response,
mastectomy was associated with worse overall
survival before matching (
hazard ratio, 2.17; 95% CI 1.22-3.86; P < 0.01) and after matching (
hazard ratio, 2.12; 95% CI 1.15-3.89; P = 0.02). Among
patients with pathological complete response in the
breast, the
survival results did not differ significantly between BCT and
mastectomy patients. IPTW
method validated that BCT offers better overall
survival in
patients who had axillary
lymph node pathological complete response.
Interpretation:
People with HER2-positive
breast cancer who have already had PST are more likely to survive after BCT, especially if they get a pathological complete response in the axillary
lymph nodes. These findings underscore the necessity for further investigation into how responses to PST can inform the choice of surgical intervention and the potential impact on overall
survival. Such insights could
lead to the development of innovative tools that support personalized surgical
strategies in the management of
breast cancer.
Funding:
This
work was supported by
grants from the Nantong
Science and
Technology Project (JCZ2022079), Nantong
Health Commission Project (QA2021031, MSZ2023040) and National
Natural Science Foundation of
China (No. 82394430).