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• W2102035300 abstract "Criscitiello et al. [1.Criscitiello C. Azim Jr, H.A. Agbor-Tarh D. et al.Factors associated with surgical management following neoadjuvant therapy in patients with primary HER2-positive breast cancer: results from the NeoALTTO phase III trial.Ann Oncol. 2013; 24: 1980-1985Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar], reporting on the NeoAdjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) trial, elegantly analyse multiple factors which might account for why high objective clinical tumour response and pathological complete response (pCR) rates did not translate into higher breast-conserving surgery (BCS) and correspondingly lower mastectomy rates. First, no information on baseline (i.e. pre-study) BCS rates for the recruiting centres was provided. As nearly half (46%) of the patients were treated in developing countries [1.Criscitiello C. Azim Jr, H.A. Agbor-Tarh D. et al.Factors associated with surgical management following neoadjuvant therapy in patients with primary HER2-positive breast cancer: results from the NeoALTTO phase III trial.Ann Oncol. 2013; 24: 1980-1985Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar], lack of optimal radiotherapy resources was proposed as a possible contributory factor but this seems unlikely, as participation in NeoALLTO [2.Baselga J. Bradbury I. Eidtmann H. et al.NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial.Lancet. 2012; 379: 633-640Abstract Full Text Full Text PDF PubMed Scopus (1014) Google Scholar] would require an adequate radiotherapy service. However, lack of access could have influenced patients' choices. An additional factor was thought to be lack of multidisciplinary meetings implying surgical decision-making without dialogue between the radiology, oncology and surgical teams and regardless of clinical tumour response. Many surgeons claim that excising the original tumour bed, i.e. the ‘footprint’ present before chemotherapy, with a margin is mandatory, on the basis of historic pre-trastuzumab studies demonstrating HR-ve, HER2+ tumours to have the highest local recurrence (LR) rates [3.Lowery A.J. Kell M.R. Glynn R.W. et al.Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype.Breast Cancer Res Treat. 2012; 133: 831-841Crossref PubMed Scopus (278) Google Scholar]. The use of targeted anti-HER2 therapy in combination with cytotoxics (especially taxanes) has mitigated the LR increase [4.Semiglazov V. Eiermann W. Zambetti M. et al.Surgery following neoadjuvant therapy in patients with HER2-positive locally advanced or inflammatory breast cancer participating in the NeOAdjuvant Herceptin (NOAH) study.Eur J Surg Oncol. 2011; 37: 856-863Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar] although long-term data are still lacking. Furthermore, there may be reluctance among surgeons to employ oncoplastic BCS techniques due to paucity of literature specifically addressing oncological safety in the neoadjuvant setting [5.Haloua M.H. Krekel N.M. Winters H.A. et al.A systematic review of oncoplastic breast-conserving surgery: current weaknesses and future prospects.Ann Surg. 2013; 257: 609-620Crossref PubMed Scopus (136) Google Scholar]. In developing countries, limited numbers of specialist breast surgeons and unfamiliarity with oncoplastic BCS techniques by general surgeons may be relevant. In NeoALLTO, the mismatch between radiological response and extent of surgery may reflect the presence of DCIS beyond the invasive component. For the purposes of randomisation, T status is determined by the extent of invasive disease so any associated DCIS cannot be easily controlled for. While it is well recognised that anti-HER2 regimes including trastuzumab can cause regression of associated HER2+ DCIS, micro-calcifications remain unchanged [6.von Minckwitz G. Darb-Esfahani S. Loibl S. et al.Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer—results from the GeparQuattro study (GBG 40).Breast Cancer Res Treat. 2012; 132: 863-870Crossref PubMed Scopus (37) Google Scholar]. Perhaps final surgery was determined by the extent of micro-calcifications rather than invasive tumour response. Despite pCR (defined in NeoALLTO as complete disappearance of invasive tumour), the reason for mastectomy was possibly residual DCIS. The disconnect between tumour response and final surgery is also exemplified by the 25.8% conversion to mastectomy (n = 33) when BCS was planned at diagnosis, despite progressive disease by imaging criteria being documented in only 11 patients. Perhaps some of these patients had lobular histology (n = 17, all of whom ended up with mastectomy) and were incompletely staged at initial assessment (possibly due to lack of MRI access). Similarly, 75% of patients with multifocal/multicentric tumours at baseline who assessment underwent mastectomy (n = 36) may never have had surgical down-staging as the intended outcome. For lobular histology, pCR rates are variable ranging from zero [7.Untch M. Rezai M. Loibl S. et al.Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study.J Clin Oncol. 2010; 28: 2024-2031Crossref PubMed Scopus (426) Google Scholar] up to 50% when adjusted for molecular subtypes such as HR-ve, HER2+ [8.Untch M. Fasching P.A. Konecny G.E. et al.Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG Study Groups.J Clin Oncol. 2011; 29: 3351-3357Crossref PubMed Scopus (400) Google Scholar]. Clinician/surgeon scepticism regarding the utility of neoadjuvant therapy for lobular disease may account for the 100% mastectomy rate seen. ER-negative status seemed to predict an increased likelihood of mastectomy even when controlled for all other known tumour factors. Paradoxically, as the authors note, this is despite a higher pCR rate for ER-veHER2+ve tumours. Surgeons possibly perceive BCS for ER-ve tumours to be a riskier option due to the lack of long-term endocrine therapy options: this observation is speculative and should be further explored. Finally, there is no mention of patient preference for mastectomy. Patient choice may not always relate to treatment response and should be recorded prospectively in all such trials where an end point is BCS rate. Regular dialogue between pathology, radiology, oncology and surgery teams either in MDM's or dedicated joint neoadjuvant clinics is crucial to optimise extent of surgery without compromising local control. The authors have declared no conflicts of interest." @default.
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• W2102035300 title "Letter to the editor on ‘Factors associated with surgical management following neoadjuvant therapy in patients with primary HER2-positive breast cancer: results from the NeoALTTO phase III trial’" @default.
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