Guest blog: a novel fluorescence technique for detecting breast cancer

Exploring psychological consequences for BRCA+ women in the post-Covid era

Whilst the global female population has a 12.5% overall lifetime risk of developing breast cancer and a 1.3% risk of ovarian cancer (Howlader et al), the risk for those with a pathogenic BRCA1 or BRCA2 mutation is 60-70% and 10-20% respectively (van Egdom et al). BRCA1 mutation carriers have a particularly high incidence of triple-negative breast cancer (TNBC) (Greenup et al) for which treatment options are more limited and always include chemotherapy (Bianchini et al; Collignon et al). 

In the NHS, asymptomatic women with at least a 10% estimated chance of having a BRCA mutation are offered testing (NICE).  Knowing you are at high risk of breast cancer and the increased likelihood of TNBC is a well-documented  cause of anxiety (Wenzel et al) and many women describe having a BRCA gene mutation as living with a ‘ticking time bomb’. Bilateral mastectomy with or without reconstruction is the only proven method of drastically decreasing risk and can improve quality of life (McCarthy et al) and decrease anxiety (Rebbeck et al) for correctly selected cases, despite its potential negative outcomes (Gahm et al). 

Invasive lobular breast cancer is the second most common histological subtype and constitutes around 10-15% of all breast cancer. It is recognized by a peculiar diffuse growth pattern and disseminated spread of cancer cells contributing to diagnostic delay and difficulties in detecting the primary tumors by mammography and nodal metastasis by axillary ultrasound. Consequently, although invasive lobular breast cancer mainly displays a favorable luminal A molecular subtype, it is often diagnosed at a higher stage than invasive cancer of no special type. Despite these characteristics, histopathological subtype is not accounted for in Clinical Guidelines, in contrast to the molecular subtypes. In the BJS publication “The St. Gallen 2019 Guidelines understage the Axilla in Lobular Breast Cancer: a Population-Based Study” by Ulrik Narbe and co-authors, we have elaborated on the consequences for patients with invasive lobular cancers if completion axillary clearance would be omitted in patients with 1-2 nodal metastases.

For the breast surgeon, lobular cancer poses a challenge to surgery of the breast and to the axilla. Large tumor size and diffuse infiltrating margins are associated with an increased risk of positive margins after breast conserving surgery and in breast centers where MRI is available, complementary imaging is recommended ahead of primary surgery. Still a larger proportion of patients (66%) with lobular cancer undergo a mastectomy compared to other histological subtypes (43%) according to our registry study, supporting previous publications. So the dogma of de-escalating breast surgery from mastectomy to partial mastectomy in lobular cancer is challenging, keeping in mind that positive resection margins is a mandatory quality criteria in most centers pushing the choice of initial surgery towards upfront mastectomy.

Axillary surgery is moving towards de-escalation of surgical interventions for patients with 1-2 sentinel node metastases after the results of the Z0011 trial have been implemented worldwide and clearly supports that omission of completion axillary dissection is non-inferior provided the inclusion criteria for the trial is fulfilled. The Z0011 criteria for omission of completion axillary dissection is restricted to patients undergoing breast-conserving surgery, and is thus not applicable for lobular cancers operated by mastectomy. The St. Gallen 2019 guidelines extended the indication for abstaining completion axillary dissection to all patients of any tumor size irrespective of type of breast surgery. In addition, the guidelines recommended that the decision on adjuvant chemotherapy for luminal A-like tumors should include nodal staging and patients with 4 or more nodal metastasis (nodal stage II) were recommended adjuvant chemotherapy. For these patients there is hitherto no data on the role of genomic tests for risk stratification until the results of OPTIMA trial are presented. In this paper, we present data from the National Swedish Quality Registry with prospectively collected data retrieved from the period when a completion axillary clearance for patients with sentinel node metastases was recommended. We found a strong association between invasive lobular breast cancer and nodal stage II disease independent of other determinants such as tumour size.

In recent years there has been an increasing focus on the evaluation of medical devices. Approval of medical devices for clinical use is approached in a different way from medicines; they require a demonstration of safety when implanted, but require little in the way of prospective evidence for their efficacy. Once a device is approved by a regulatory authority it can be used by clinicians without mandate for further research or audit on the product. This has inevitably led to manufacturers marketing their products to clinicians, often with little or no published evidence as to their efficacy. Historically, the introduction of devices following regulatory approval has taken a path many of us would have witnessed; a few early adopters work with the manufacturer to develop a small series, often in multiple centres, in a disjointed manner. Hence, over time a novel device may be supported by several small case series, performed in potentially biased sites. These series are often reported with inconsistent outcome measures and differing methodology. The majority of these studies would not have a control group for comparison, making it difficult to establish the true benefits or harms of this novel device.

This approach has inherent drawbacks for both manufacturers, and for surgeons and patients. Manufacturers may often support a series of small studies at moderate cost, which can be slow to deliver and/or be published. The data generated are often not directly comparable or able to be analysed collectively. With regards to patients; Is it right to place a device for which you have no outcome data? Is it right to place a device without consenting that you are new to using this device, with little known about its outcomes? Lastly, why would surgeons use a novel device with little evidence base? There are clearly a multitude of reasons; the device may be an improvement from established practice, there may be pressure from manufacturers, and they may be driven by the desire to be the first to use a device, along with the potential kudos for publishing or presenting on the subject.

The iBRA-NET was established to find a better way of evaluating devices new to the market. As a collaborative group we wished to establish a framework for research and audit of outcomes of new devices, with a robust governance structure. There was an imperative need to study localisation devices for impalpable breast cancers, due to their rapid introduction into the clinical setting, and the relatively short-term follow-up requirements meant that this was a deliverable study. The manuscript sets out how we established a prospective national study to evaluate all new breast localisation devices, comparing these to the historical standard of wire localisation. The simple aims of the study were to provide patients, clinicians and manufacturers with robustly-audited outcomes for these localisation devices, and to provide a platform for shared learning on device usage, with oversight of this evaluation from a body of professionals committed to the safe introduction of surgical devices.