The unifying concepts of the sick lobe hypothesis, field cancerisation and breast conservation treatment for multiple ipsilateral breast cancers: a narrative review.

Background and Objective: In the past, it was conventionally thought that multiple ipsilateral breast cancer (MIBC) was a contraindication to breast conservation surgery, especially if multicentric foci in different quadrants of the breast were present. However, over time, there has been a growing body of evidence in the literature demonstrating no survival detriment or poorer local control with breast conservation for MIBC. There is, however, a paucity of information integrating anatomy, pathology with surgical treatment of MIBC. Understanding mammary anatomy, pathology of the sick lobe hypothesis and molecular impact of field cancerisation contributes significantly to the understanding of the role of surgical treatment of MIBC. The purpose of this narrative overview is to review the paradigm shifts over time in the use of breast conservation treatment (BCT) for MIBC, and how the concepts of the sick lobe hypothesis and field cancerisation interact with this therapeutic strategy. A secondary objective is to explore the feasibility of surgical de-escalation for BCT in the presence of MIBC. Methods: A PubMed search was performed for articles relating to BCT, multifocal, multicentric and MIBC. A separate literature search was performed for sick lobe hypothesis and field cancerisation and their interaction for surgical treatment for breast cancer. The available data was then analysed and synergised into a coherent summary of how the molecular and histologic aspects of MIBC interact with surgical therapy. Key Content and Findings: There is a growing body of evidence supporting the use of BCT for MIBC. However, there is scant data connecting the basic science aspects of breast cancer in terms of pathology and genetics to adequacy of surgical extirpation of breast malignancies. This review bridges this gap by demonstrating how information on basic sciences available in contemporary literature can be extrapolated for use in artificial intelligence (AI) systems to assist in BCT for MIBC. Conclusions: This narrative review connects several aspects of the surgical treatment for MIBC: historical perspectives of therapy compared with contemporary philosophy based on clinical evidence, anatomy/pathology (sick lobe hypothesis) and molecular findings (field cancerisation) as potential indicators of adequate surgical resection, and how current technology can be used to forge future AI applications in breast cancer surgery. These form the foundation for future research to safely de-escalate surgery for women with MIBC.

The challenge of equipoise: qualitative interviews exploring the views of health professionals and women with multiple ipsilateral breast cancer on recruitment to a surgical randomised controlled feasibility trial.

BACKGROUND: A multicentre feasibility trial (MIAMI), comparing outcomes and quality of life of women with multiple ipsilateral breast cancer randomised to therapeutic mammoplasty or mastectomy, was conducted from September 2018 to March 2020. The MIAMI surgical trial aimed to investigate recruitment of sufficient numbers of women. Multidisciplinary teams at 10 breast care centres in the UK identified 190 with MIBC diagnosis; 20 were eligible for trial participation but after being approached only four patients were recruited. A nested qualitative study sought to understand the reasons for this lack of recruitment. METHODS: Interviews were conducted from November 2019 to September 2020 with 17 staff from eight hospital-based breast care centres that recruited and attempted to recruit to MIAMI; and seven patients from four centres, comprising all patients who were recruited to the trial and some who declined to take part. Interviews were audio-recorded, anonymised and analysed using thematic methods of building codes into themes and sub-themes using the process of constant comparison. RESULTS: Overarching themes of (1) influences on equipoise and recruitment and (2) effects of a lack of equipoise were generated. Within these themes, health professional themes described the barriers to recruitment as 'the treatment landscape has changed', 'staff preferences and beliefs' which influenced equipoise and patient advice; and how different the treatments were for patients. Patient themes of 'altruism and timing of trial approach', 'influences from consultants and others' and 'diagnostic journey doubts' all played a part in whether patients agreed to take part in the trial. CONCLUSIONS: Barriers to recruiting to breast cancer surgical trials can be significant, especially where there are substantial differences between the treatments being offered and a lack of equipoise communicated by healthcare professionals to patients. Patients can become overwhelmed by numerous requests for participation in research trials and inappropriate timing of trial discussions. Alternative study designs to the gold standard randomised control trial for surgical interventions may be required to provide the high-quality evidence on which to base practice. TRIAL REGISTRATION: ISRCTN ( ISRCTN17987569 ) registered on April 20, 2018, and ClinicalTrials.gov ( NCT03514654 ).

Evaluating the current evidence to support therapeutic mammoplasty or breast-conserving surgery as an alternative to mastectomy in the treatment of multifocal and multicentric breast cancers.

The oncological safety of treating multiple ipsilateral breast cancers (MIBCs) with types of breast conserving surgery (BCS) compared to mastectomy remains uncertain. This is predicated on the absence of any randomised controlled trials or high-quality protocol defined prospective cohort studies. A single recently published systematic review by the first author, reports its summarised results in this review. Fundamentally the important question is the evaluation of clinical safety following BCS compared to mastectomy for treating MIBC, which is reported in only six studies. Consequently, current evidence doesn't support the latest St Gallen consensus suggesting the possibility of using BCS to treat all MIBC. There is minimal comparative outcomes data on multicentric (MC) cancers compared to multifocal (MF) cancers comparing BCS or mastectomy. There is also poor evidence of clinical outcomes following therapeutic mammoplasty (TM) for MIBC compared to mastectomy. The potential recommendation of two potential radiotherapy boosts to separate lumpectomy sites following BCS for MC cancers remains a novel treatment concept whose feasibility will be evaluated in the forthcoming NIHR funded randomised feasibility trial called MIAMI. This is a world first attempt to assess the feasibility of a randomised trial design alongside the on-going Alliance registry study (ACOSOG, American College of Surgeons Oncology Group Z11102) in the USA, in which there is no comparative evaluation of mastectomy outcomes. The MIAMI trial aims to assess the clinical safety of multiple lumpectomies combined with TM compared to the standard of mastectomy in MIBC stratified by MF or MC cancers. There is limited evidence on the impacts of inter-tumoral heterogeneity relating to breast cancer subtypes in relation to individualised treatments and recommendations for types of breast surgery. Recent studies have highlighted the potential contributions of stromal epigenetic changes that are currently poorly understood regarding their contributions to either clinical unifocal or MF cancers.