Re: Rethinking neoadjuvant chemotherapy for breast cancer
Vaidya et al defend their opinions on neoadjuvant chemotherapy with seemingly ill-thought out views.
1. The EBCTCG analysis is outdated as are many of the EBCTCG analyses. However, far from "rubbishing" the analysis we are stressing the importance of considering historical absolute rates of recurrence in the light of current practice. Systemic therapies, whose introduction post-dates the meta-analysis, reduce local-regional as well as distant recurrences. We would not use the figures on local recurrence after breast conservation from the EBCTCG analysis to counsel patients in 2018. Recurrence rates have changed dramatically and we counsel patients with current data.
2. Few patients do not respond to chemotherapy. Women understand the benefits of a responding tumour. The stress of living with a cancer in their breast is manageable and is managed by the multidisciplinary team. In the very few with failure to respond there is the opportunity to switch therapy or to perform surgery. The view that NACT has a negative impact on survival is not supported by evidence.
3. The authors quote a few but not all studies of NACT. Generally, increasing HR for pCR does increase the HR for EFS and OS.
4. The section on tumour marking is perhaps the most perplexing. Once a clip is placed in a large tumour it does stay where it is. Migration happens in smaller cancers immediately after placement. If the marker is not in a satisfactory position a second marker can be placed. Vaidya et al seem to have learned nothing from the lesions of yesteryear and surely must recognise that more extensive surgery has never been shown to improve overall survival. Vaidya and colleagues seem not to have read studies like BO4 where leaving axillary nodes did not influence overall survival. The direction of travel is clear and it is not in the direction of Vaidya and colleagues.
5. Vaidya and colleagues accept testing for BRCA1 and 2 genes is logical but then do not understand how this information can be integrated with knowledge about response to chemotherapy to plan more appropriate treatments for individual patients.
6. Vaidya and colleagues do not see the flaws in their own arguments. On the one hand they emphasise the stress of a patient having a cancer left in her breast and later they dismiss breast reconstruction because it may delay systemic therapy.
7. Vaidya on the one hand accepts that NACT is no worse but on the other hand indicates NACT may increase cancer cell dissemination which would surely make survival worse?
8. While Vaidya and Benson state that breast conservation is possible in only a small percentage of patients the numbers who are in fact eligible for breast conservation is much greater. It is because MDTs are poor at assimilating response data and making the correct decision. The majority of patients in the units in which we work are suitable for BCT after NACT. The rates of conversion reported by Vaidya quoted in the outdated ECBTCG analysis bear no resemblance to the rate ratio we now see. For example, we have shown conversion from obligate mastectomy to breast conserving surgery in 62% of patients .
9. The benefits of downstaging are not only confined to the breast but include sparing patients with proven node positive disease axillary clearance with its associated morbidity in the event of nodal pCR. Improvements in technique with clipping of the involved node and removal of at least 3 nodes following dual mapping give acceptable false negative rates of >10%. Overall nodal pCR rates range from 35-49% but can be as high as 97% in ER-/HER2+ patients treated with dual blockade. As with conversion to breast conserving surgery patient selection is the key; a recent review of practice by Pilewskie et al. showed a significant reduction in ALND rates in HER2+ and TN breast cancer but not ER+/HER2- disease where axillary clearance rates were paradoxically higher in the neoadjuvant setting if Z0011 criteria are used .
Thankfully the views of Vaidya and colleagues are not shared by the majority of surgeons and oncologists managing women with breast cancer who will continue to explore the significant value of NACT in modern day management of breast patients.
Prof J Michael Dixon OBE, Professor of Surgery and Consultant Surgeon, Edinburgh Breast Unit, Western General Hospital, Edinburgh.
Dr Iain R Macpherson, Clinical Senior Lecturer in Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow
Mr Henry Cain, Consultant Oncoplastic Breast Surgeon, Royal Victoria Infirmary, Newcastle
Dr Caroline Michie, Consultant in Clinical Oncology, Edinburgh Cancer Centre, Western General Hospital, Edinburgh.
Dr Elena Provenzano - Lead Consultant Breast Pathologist, Addenbrookes Hospital and NIHR Cambridge Biomedical Research Centre, Cambridge.
1. Pieri A, Whyte E, Cain H. Outcomes following neoadjuvant chemotherapy: converting trial results into "real world" practice, European Journal of Surgical Oncology 2017, 43(5): S58
2. Pilewskie M, et al. The Optimal Treatment Plan to Avoid Axillary Lymph Node Dissection in Early-Stage Breast Cancer Patients
Competing interests: IM, HC - paid membership of advisory board, travel and accommodation for Roche Products UK Ltd. IM - paid membership of advisory board for Genomic Health.