The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making

Abstract

Background Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. Methods Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item. Results Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5–60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0–25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. Discussion There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes.

Is local recurrence higher among patients who downstage to breast conservation after neoadjuvant chemotherapy?

“…The perception that all breast tissue initially involved by the tumor must be excised at the time of surgery may lead to unnecessary mastectomies in this setting. 13,14 Although guidelines such as those published by the St. Gallen International Expert Consensus advise that resection of the entire tumor bed after neoadjuvant treatment is not necessary, 15 practice remains highly variable. In a recent survey of all multidisciplinary teams from breast units in the United Kingdom, 26% of centers reported resection of the original tumor footprint, regardless of clinical and radiologic responses.…”

“…In a recent survey of all multidisciplinary teams from breast units in the United Kingdom, 26% of centers reported resection of the original tumor footprint, regardless of clinical and radiologic responses. 13 Similarly, in the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (NeoALLTO) trial of neoadjuvant treatment for HER2+ cancers, despite dramatic improvements in pCR rates with dual HER2 blockade, BCS rates did not increase, and the use of BCS remained most frequent among those who were deemed BCSe at diagnosis. 16 However, data from past studies, including a retrospective study of 509 consecutive patients with T1-3N0-2 cancers treated in prospective trials of chemotherapy from 1998 to 2005, have demonstrated the safety of limiting resection to residual viable tumor.…”

Innovative Standards in Surgery of the Breast after Neoadjuvant Systemic Therapy

“…A survey of British breast cancer teams reported that 74% of centers practice response-adapted surgery, whereas 26% stated that they resect the original tumor footprint [25]. The 2017 St. Gallen consensus panel voted on de-escalation of surgery after NST: 82% of panelists voted that surgical resection should include only the post-NST extent of the tumor, and only 14% voted that the original (pretreatment) tumor bed needs to be excised [26].…”

“…A common indication for NET is to convert mastectomy to BCS, although this is achieved at lower rates than NAC [25]. Semiglazov et al reported a phase 2 trial of NET compared with NAC in 239 postmenopausal patients with ER-positive breast cancer, all ineligible for BCS at diagnosis.…”

Tumor Glucose and Fatty Acid Metabolism in the Context of Anthracycline and Taxane-Based (Neo)Adjuvant Chemotherapy in Breast Carcinomas

“…Neoadjuvant systemic therapy (NeST) is routinely used to treat breast cancer, with significant geographical variation in its use across different countries ( 1 , 2 ). When introduced, NeST was used mostly for the treatment of patients with locally advanced or inoperable breast cancer aiming to reduce the tumor size, enabling post-therapy breast-conservation surgery.…”