Neoadjuvant chemotherapy in breast cancer: more than just downsizing
A partir des données de 10 essais randomisés incluant 4 756 patientes atteintes d'un cancer du sein de stade précoce et incluses entre 1983 et 2002 (durée médiane de suivi : 9 ans), cette méta-analyse compare l'intérêt, du point de vue de la réponse tumorale, de l'amélioration de la faisabilité et de l'efficacité d'un traitement chirurgical, du risque de récidive, de la mortalité spécifique et de la mortalité globale, d'une chimiothérapie néoadjuvante et d'une chimiothérapie adjuvante
The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) has established a new milestone in evidence-based treatment for early breast cancer. Through longstanding collaboration, mutual trust, and data transparency, they have gathered individual patient data for 4756 women randomly allocated in ten trials to either neoadjuvant chemotherapy (NACT) or adjuvant chemotherapy, with a median follow-up of 9 years (IQR 5–14). The results of this meta-analysis, published in The Lancet Oncology, substantiate that NACT results in higher rates of breast-conserving therapy than does adjuvant chemotherapy (rate ratio 1·28 [95% CI 1·22–1·34]), without compromising on distant recurrence, breast cancer survival, or overall survival.
Much emphasis is given by the authors to an increase in local recurrence in the NACT group (15 year absolute increase of 5·5% [95% CI 2·4–8·6]). Whether NACT itself could be held accountable for the small increase in local recurrences is questionable. Higher local recurrence with breast-conserving surgery than with mastectomy is inherent to breast-conserving therapy. The meta-analysis by Mieog and colleagues showed no significant difference in local recurrence between patients receiving breast-conserving surgery after NACT and breast-conserving surgery followed by adjuvant chemotherapy, even with inclusion of those receiving NACT that were initially scheduled for mastectomy.
In the meta-analysis by the EBCTCG, NACT led to response of the primary tumour, which undoubtedly led to concomitant downstaging of the axillary lymph nodes. Unfortunately, the EBCTCG was not able to collect data for lymph node status before and after neoadjuvant treatment in these trials. Moreover, axillary treatment strategies have drastically changed in the last two decades, making interpretation of older findings difficult. Probably for these reasons, downstaging of lymph node status was not discussed in the Article. Axillary lymph node dissection is associated with substantial long-term morbidity and is often considered to be worse than morbidity caused by breast surgery. Studieshave shown that pathological complete response (pCR) of the axilla is achieved in 41–75% of patients with HER2-positive or triple-negative cancer receiving NACT. Especially among patients with an ultrasound-positive or cytological-positive axilla who had a clinical response with downstaging to a negative axilla, controversy still exists regarding the timing and accuracy of nodal staging with sentinel lymph node biopsy.
Several studies have addressed the accuracy of nodal staging after NACT and current consensus is that sentinel lymph node biopsy after NACT in patients with initial positive axilla is considered accurate if at least three or more sentinel nodes are detected and examined.
Although the willingness of surgeons to omit axillary lymph node dissection or radiotherapy of the axilla in patients with complete response to NACT is high, no studies have yet investigated locoregional outcomes. A randomised phase 3 trial is ongoing to assess the role of axillary radiotherapy versus no axillary radiotherapy in patients who converted to pathologically node-negative disease after NACT.
The Lancet Oncology , commentaire en libre accès, 2016