Breast conservation surgery and mastectomy have similar locoregional recurrence following neoadjuvant chemotherapy: results from over 1400 patients on the prospective, randomized I-SPY2 Trial
Rita Mukhtar*1, Harrison Chau3, Hannah Woriax4, Mara Piltin2, Gretchen Ahrendt5, Julia Tchou6, Hongmei Yu7, Qian Ding7, Catherine L. Dugan1, Jori Sheade8, Angelena Crown21, Michael Carr9, Jasmine Wong1, Jennifer Son10, Rachel Yang1, Theresa Chan11, Alicia Terando12, Michael Alvarado1, Cheryl Ewing1, Jennifer Tonneson13, Nina Tamirisa14, Rebekah Gould14, Puneet Singh14, Constantine Godellas15, Kelsey Larson16, Akiko Chiba4, Roshni Rao17, Kathy Czaplicki18, Lauren Postlewait19, Marie C. Lee20, William F. Symmans14, Laura Esserman1, ISPY-2 Locoregional Working Group1, Judy Boughey2
1University of California San Francisco, San Francisco, CA; 2Mayo Clinic, Rochester, MN; 3University of California San Diego, San Diego, CA; 4Duke University Medical Center, Durham, NC; 5University of Colorado, Aurora, CO; 6University of Pennsylvania, Philadelphia, PA; 7Quantum Leap Healthcare, San Francisco, CA; 8Northwestern Medicine, Chicago, IL, IL; 9University of Louisville, Louisville, KY; 10Georgetown University, Washington, ; 11Ironwood Cancer and Research Centers, Phoenix, AZ; 12Cedars-Sinai Cancer at Huntington Hospital Cancer Center, Pasadena, CA; 13Oregon Health and Science University, Portland, OR; 14University of Texas MD Anderson Cancer Center, Houston, TX; 15Ascension Medical Group, Elk Grove Village, IL; 16University of Kansas, Kansas City, KS; 17Columbia University, New York, NY; 18Loyola University Medical Center, Maywood, IL; 19Emory University, Atlanta, GA; 20Moffitt Cancer Center, Tampa, FL; 21Swedish Cancer Institute, Seattle, WA
Neoadjuvant chemotherapy (NAC) increases rates of successful breast conserving surgery (BCS) in patients with breast cancer who would otherwise require mastectomy based on disease extent at diagnosis. However, some studies have suggested that BCS after tumor down-staging with NAC may be associated with increased risk of locoregional recurrence (LRR), with conflicting results in the literature. The aim of this study was to assess LRR rates following NAC and determine if type of surgery impacts LRR.
We analyzed outcomes of all patients enrolled on the I-SPY2 trial, an adaptive, multicenter trial enrolling patients with clinical stage II-III, molecularly high-risk primary breast cancer treated with NAC followed by surgery from 2010-2021. We evaluated the impact of type of surgery (BCS vs mastectomy) on time to locoregional recurrence (LRR). Cox proportional hazards models were used to evaluate the associations between surgical procedure, patient age, tumor receptor subtype, clinical stage, and Residual Cancer Burden (RCB) with time to LRR. RCB was bimodally categorized as classes 0 and 1 (pathologic complete response, pCR, or minimal residual invasive disease), or classes 2 and 3 (significant residual invasive disease).
Of 1,478 patients, 644 (43.6%) underwent BCS and 834 (56.4%) underwent mastectomy. Overall pCR was 35.9% and varied between the two groups (41.7% in those with BCS and 31.5% in those with mastectomy) Those undergoing mastectomy were more often <50 years of age (62.0% vs 49.9%, p<0.0001), clinical stage III (72.0% vs 28.0%, p<0.0001), and more likely to have RCB class 2/3 disease on final pathology (63.0% vs 37.0%, p<0.0001). Median follow up time was 3.5 years (range 0.4-10.2). In total 91 patients (6.2%) experienced a LRR event. In univariate and multivariate analyses, the surgical procedure performed was not associated with LRR. The unadjusted incidence of LRR was 5.4% in those undergoing BCS, and 6.7% in those undergoing mastectomy (p=0.28, log rank). The strongest predictor of LRR was RCB class (adjusted hazard ratio [HR] for RCB 2/3 compared to 0/1 was 5.64, 95% confidence interval 3.19-9.99, p<0.0001, Table).
In this large multi-institutional prospective clinical trial of patients with high-risk breast cancer completing NAC over the last decade we found no increased risk of LRR following BCS compared to mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that breast conservation surgery is an excellent surgical option for patients after NAC in appropriately selected patients.
Table 1. Multivariate Cox Proportional Hazards Regression for Local Recurrence Outcome
|>=50 yrs||0.84 (0.55, 1.30)||0.44|
|HR-Her2-||2.56 (1.58, 4.13)||0.0001|
|Her2+||1.15 (0.61, 2.18)||0.66|
|III||1.56 (0.98, 2.49)||0.06|
|Mastectomy||0.94 (0.60, 1.47)||0.78|
|2/3||5.64 (3.19, 9.99)||<.0001|
HR: Hazard Ratio, CI: Confidence Interval.
Figure 1. Kaplan-Meier Plot Stratified by Surgery and RCB Category for Local Recurrence
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