Abstract P2-16-04: National utilisation of neoadjuvant systemic therapy and impact on surgical treatment - A prospective multi-centre cohort study
Authors: McIntosh Stuart A , Irwin Gareth W , Bannon Finian , Coles Charlotte , Copson Ellen , Cutress Ramsey , Dave Rajiv , Grayson Margaret , Holcombe Chris , Irshad Sheeba , O'Brien Ciara , O'Connell Rachel , Palmieri Carlo , Shaaban Abeer M , Sharma Nisha , Singh Jagdeep , Whitehead Ian , Potter Shelley 
Published: March 2020

Introduction: Potential advantages of neoadjuvant systemic therapy (NST) include downstaging disease to minimise surgery, and in vivo assessment of tumour sensitivity to therapeutic drugs. Considerable variation in NST use remains, however, and it is unclear whether pathological response rates reflect those reported in trials, or whether downstaging achieved impacts on surgical decision-making. The NeST prospective multicentre study will address these questions through investigating patterns of care in the UK.

Methods: Women undergoing NST as their primary breast cancer treatment (chemotherapy (CT), endocrine (ET) and targeted therapies) in UK centres between December 2017 and November 2018 were included. Anonymised data was collected at 37 participating centres, and uploaded to REDCap.

Results: 1179 patients received neoadjuvant treatment during the study period. 41% had HER2+ disease, 28% TNBC and 31% ER+ HER2- disease. 48% were node positive and 52% node negative. Cited indications for neoadjuvant treatment were (more than one option applicable to each patient):

Downstaging (mastectomy to breast conservation) 37%

Facilitate dual antiHER2 therapy 33%

Inoperable disease 19%

Improved cosmesis (reduced volume of excision) 17%

Facilitate BRCA testing 9%

Inflammatory breast cancer 6%

In patients recommended to receive NST, the MDT decision was for neoadjuvant CT in 87% of cases and neoadjuvant ET in 13%. For ER+ disease, the commonest reasons for prescribing CT were high grade disease and pre-menopausal status. The majority were treated with anthracycline-taxane combinations. 21% of TNBC patients were treated with platinum-containing regimens. In HER2+ disease, 54% were treated with dual antiHER2 therapies/chemotherapy, with 10% receiving chemotherapy/single antiHER2 agent (trastuzumab).

Centres were asked to indicate primary breast surgical treatment recommended prior to/without NST. At abstract submission, this data was available for 887 patients. 31 had inoperable disease. A total of 477 were considered to require mastectomy, with disease not amenable to breast conservation surgery (BCS). A further 379 patients were considered candidates for BCS. Data on final surgical procedure was available for 765 patients. Of those patients determined suitable only for mastectomy at diagnosis, 123 underwent BCS as their primary operation - a downstaging rate of 26%. The overall mastectomy rate in this cohort was 48%, with 33% having mastectomy and 15% mastectomy with immediate reconstruction.

Pathological response data was available in 672 patients, with an overall pathological complete response (pCR) rate of 29% (defined as no residual invasive or in situ disease). pCR rate according to molecular subtype was 37% for HER2+ disease, 35% for TNBC and 7% for ER+, HER2-ve disease. The pCR rate in patients downstaged from mastectomy to BCS was 27%.

Conclusions: This UK national prospective study suggests that surgical downstaging remains a key indication for the use of NST. This is reflected in the fact that 26% of patients in this series were downstaged from an original surgical plan for mastectomy, with NST enabling BCS in these patients. However, based on this data it appears that surgical downstaging is no more likely in those with pCR compared to those without a pCR.

Additional indications for NST are emerging, according to disease biology. There is widespread use of dual antiHER2 targeted therapies in this setting, with increasing use of platinum-containing regimens for TNBC. Neoadjuvant CT continues to be frequently used in the treatment of ER+ disease, despite known low pCR rates in this context, which are again confirmed. Low rates of neoadjuvant ET use are reported.

Data collection is ongoing; updated data will be presented in December 2019.

Citation Format: Stuart A McIntosh, Gareth W Irwin, Finian Bannon, Charlotte Coles, Ellen Copson, Ramsey Cutress, Rajiv Dave, Margaret Grayson, Chris Holcombe, Sheeba Irshad, Ciara O'Brien, Rachel O'Connell, Carlo Palmieri, Abeer M Shaaban, Nisha Sharma, Jagdeep Singh, Ian Whitehead, Shelley Potter. National utilisation of neoadjuvant systemic therapy and impact on surgical treatment - A prospective multi-centre cohort study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-04.