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Clinical Trial
. 2021 May 27;108(5):583-589.
doi: 10.1002/bjs.11963.

Long-term prognosis in breast cancer is associated with residual disease after neoadjuvant systemic therapy but not with initial nodal status

L Zetterlund  1   2 , F Celebioglu  1   3 , T Hatschek  4 , J Frisell  5 , J de Boniface  2   5
Affiliations
Clinical Trial

Long-term prognosis in breast cancer is associated with residual disease after neoadjuvant systemic therapy but not with initial nodal status

L Zetterlund et al. Br J Surg. .

Abstract
in English, Spanish

Background: This follow-up analysis of a Swedish prospective multicentre trial had the primary aim to determine invasive disease-free (IDFS), breast cancer-specific (BCSS) and overall survival (OS) rates, and their association with axillary staging results before and after neoadjuvant systemic therapy for breast cancer.

Methods: Women who underwent neoadjuvant systemic therapy for clinically node-positive (cN+) or -negative (cN0) primary breast cancer between 2010 and 2015 were included. Patients had a sentinel lymph node biopsy before and/or after neoadjuvant systemic therapy, and all underwent completion axillary lymph node dissection. Follow-up was until February 2019. The main outcome measures were IDFS, BCSS and OS. Univariable and multivariable Cox regression analyses were used to identify independent factors associated with survival.

Results: The study included a total of 417 women. Median follow-up was 48 (range 7-114) months. Nodal status after neoadjuvant systemic therapy, but not before, was significantly associated with crude survival: residual nodal disease (ypN+) resulted in a significantly shorter 5-year OS compared with a complete nodal response (ypN0) (83·3 versus 91·0 per cent; P = 0·017). The agreement between breast (ypT) and nodal (ypN) status after neoadjuvant systemic therapy was high, and more so in patients with cN0 tumours (64 of 66, 97 per cent) than those with cN+ disease (49 of 60, 82 per cent) (P = 0·005). In multivariable analysis, ypN0 (hazard ratio 0·41, 95 per cent c.i. 0·22 to 0·74; P = 0·003) and local radiotherapy (hazard ratio 0·23, 0·08 to 0·64; P = 0·005) were associated with improved IDFS, and triple-negative molecular subtype with worse IDFS.

Conclusion: The present findings underline the prognostic significance of nodal status after neoadjuvant systemic therapy. This confirms the clinical value of surgical axillary staging after neoadjuvant systemic therapy.

Antecedentes: Se trata de un análisis de seguimiento en el marco de un ensayo multicéntrico prospectivo sueco con el objetivo principal de determinar las tasas de supervivencia libre de enfermedad invasiva (invasive disease‐free survival, IDFS), supervivencia específica de cáncer de mama (breast cáncer‐specific survival, BCSS) y supervivencia global (overall survival, OS) y su asociación con los resultados de la estadificación axilar antes y después de la terapia sistémica neoadyuvante para el cáncer de mama.

Métodos: Se incluyeron un total de 417 mujeres tratadas con NAST por cáncer de mama primario con ganglios clínicamente positivos (cN +) o negativos (cN0) entre 2010 y 2015. Las pacientes tenían una biopsia del ganglio linfático centinela (sentinel lymph node biopsy, SLNB) antes y/o después del tratamiento sistémico neoadyuvante y todas se sometieron a una disección completa de los ganglios linfáticos axilares. El seguimiento fue hasta febrero de 2019. Las principales medidas de resultados fueron IDFS, BCSS y OS. Se utilizaron análisis de regresión de Cox uni‐ y multivariables para identificar los factores independientes asociados con la supervivencia.

Resultados: La mediana de seguimiento fue de 48 meses (rango 7‐114). El estado ganglionar después, pero no antes, del tratamiento sistémica neoadyuvante se asoció de forma significativa con la supervivencia cruda: la enfermedad ganglionar residual (ypN +) se asoció con una OS a los 5 años significativamente más corta en comparación con la respuesta ganglionar completa (ypN0: OS 83,3 versus 91,0%, P = 0,017). La concordancia entre el estado de la mama (ypT) y de los ganglios (ypN) después de la terapia sistémica neoadyuvante fue alta, y más en cN0 (64/66, 97,0%) que en pacientes con cN + (49/60, 81,7%, P = 0,005). En el análisis multivariable, ypN0 (cociente de riesgos instantáneos, hazard ratio, HR 0,41, i.c. del 95% 0,22‐0,74, P = 0,003) y la radioterapia local (HR 0,23 (0,08‐0,64, P = 0,005)) se asociaron con un subtipo molecular triple negativo con peor IDFS.

Conclusión: Los presentes hallazgos subrayan la importancia pronóstica del estado ganglionar después de la terapia sistémica neoadyuvante. Esto confirma el valor clínico de la estadificación axilar quirúrgica después de la terapia sistémica neoadyuvante.

This long‐term follow‐up study determined survival rates in a Swedish national cohort of 417 patients with breast cancer who all had neoadjuvant systemic therapy (NAST). Sentinel lymph node biopsy (SLNB) was performed before NAST in clinically node‐negative and after NAST in clinically node‐positive patients. All patients had an axillary lymph node dissection after NAST. Axillary staging results after NAST predicted survival, supporting the practice of SLNB after NAST in all patients. pCR, pathological complete response.

SNLB better after NAST

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Figures

Fig. 1
Fig. 1
Kaplan–Meier survival curves for invasive disease‐free survival Invasive disease‐free survival according to a cN status before neoadjuvant systemic therapy (NAST) (417 patients, 94 events), b ypN status after NAST (417 patients, 94 events) and c surrogate molecular tumour subtype (416 patients, 93 events). sn, sentinel node; pCR, pathological complete response; HR, hormone receptor; HER2, human epidermal growth factor receptor 2; TNBC, triple‐negative breast cancer. a P = 0·078, b P < 0·001, c P = 0·003 (log rank test).
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