Innovations in Breast Cancer Care

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1		Muskaan Khosla	--	1966	2023-06-06 15:43:28	\|
2	update references and layout	Rita Xu	Meta information modification	1966	2023-06-07 03:39:36	\|

This entry is adapted from the peer-reviewed paper 10.3390/medicina59050957

Breast cancer care has seen tremendous advancements through various innovations to improve early detection, diagnosis, treatment, and survival. These innovations include advancements in imaging techniques, minimally invasive surgical techniques, targeted therapies and personalized medicine, radiation therapy, and multidisciplinary care.

breast cancer innovations artificial intelligence imaging

1. Introduction

Breast cancer is the commonest cancer among women and ranks as the second cause of cancer-related deaths in women ^[1]. Breast cancer care has seen significant advancements in recent years through various innovations to improve early detection, diagnosis, treatment, and survival. There have been rapid innovations in breast imaging and localization methods; genetic and genomic profiling for personalized medicine; implantable devices; and integration of artificial intelligence and deep learning models for image analysis, image-guided surgery, surgical planning, and prediction of treatment outcomes. Circumstances created by the COVID-19 pandemic have led to increased telemedicine use and have modified follow-up protocols and radiotherapy delivery methods. Additionally, with the use of more advanced prognostic and predictive tests, unnecessary/over-diagnosis, treatments, and hospital admissions ^[2]^[3]^[4] can be avoided.

2. Innovations in Breast Cancer Care

2.1. Diagnostic Innovations in Breast Imaging

2.1.1. Mammography

The standard modality for screening and diagnosing breast malignancy has been mammography since its use following the Forrest Report in 1986, which concluded that mammographic breast cancer screening was effective in reducing breast cancer mortality and recommended the establishment of a national breast cancer screening program in the UK for women aged 50 to 64 years ^[5]. This cornerstone imaging technique has undergone several advancements, which is now developing into 3D mammograms or digital breast tomosynthesis (DBT). This mammography technique captures multiple breast images from different angles to create a three-dimensional image of the breast tissue using enhanced software. It thus allows for a more detailed and comprehensive view of the breast compared to traditional 2D mammography, which captures a single image. It has been demonstrated to improve breast cancer detection rates, particularly in women with dense breast tissue. Images generated by DBT allow for the evaluation of abnormal findings, such as masses or calcifications, by providing a more detailed view of their shape, size, and location within the breast tissue. However, it has increased radiation exposure compared to 2D mammography and potentially higher costs ^[6].

In addition, contrast-enhanced mammography (CEM) is a newly emerging tool in breast radiology which uses radioiodine/contrast material to assess breast neovascularity and provides both anatomical and local changes in the breast. Some trials have now looked into the role of CEM as a tool for screening high-risk younger patients. This has been hailed as an alternative to breast MRI and is cheaper but has a higher radiation dosage ^[7].

2.1.2. Ultrasound Elastography

The role of ultrasound elastography has now been extended into identifying breast lesions. It uses ultrasound waves to generate tissue displacement or deformation images in response to external mechanical compression or vibration. These images are then analysed to assess the stiffness or elasticity of the breast tissue. Using a shear wave or strain wave pattern, one can differentiate a benign lesion from a malignant one. These techniques complement each other and work on the basic principle that focal breast malignant lesions are stiffer than benign lesions ^[8].

Guidelines recommending the use of elastography for characterizing breast lesions have been published by the European Federation of Societies for Ultrasound in Medicine (EFSUMB) and the World Federation of Ultrasound in Medicine and Biology (WFUMB) ^[9]. Both these guidelines recommend the addition of elastography to conventional ultrasound to improve the characterization of breast lesions as benign or malignant. Although a relatively newer technique, it has been used in other organs for assessment, including the thyroid, prostate, and liver.

2.1.3. Newer Ultrasound Localization Techniques

Breast localization techniques have been known to guide surgical excisions for non-palpable or occult breast lesions using clips and wires. However, more sophisticated localization techniques have been developed, which can be deployed in advance and cause minimal tissue trauma or migration issues.

Increasing use of breast conservation surgery, especially after downstaging following neoadjuvant chemotherapy (NACT), has led to an increase in the use of novel techniques such as Magseed^®, Radiofrequency Iodine seed (RFID) localization, Savi Scout^®, and Pintuition^® to assist in precisely excising tissue of interest in theatre; this coupled with the use of 3D intraoperative X-rays have greatly helped to reduce breast margin re-excision rates and improved cosmetic outcomes, leading to better patient satisfaction and reduced readmission rates. A significant advantage is the ease of inserting these localizers under local anaesthesia in outpatient settings under ultrasound guidance, and this can be kept in the breast for six months, which can help in surgical scheduling and resource optimization ^[10]^[11]^[12]^[13].

2.1.4. Outpatient Vacuum-Assisted Biopsy and Excision of Breast lesions (VAB/VAE)

The management of breast lesions with uncertain malignant potential, often called B3 lesions, is slightly complex. These lesions include lesions such as flat columnar cell atypia, atypical ductal hyperplasia (ADH), atypical intraductal epithelial proliferation (AIDEP), radial scar, papillary lesions, and lobular carcinoma in situ (LCIS) ^[14]. These lesions would often be removed with open surgical excision using a wire as a localizer in the past. This management has now changed to an outpatient procedure with vacuum-assisted biopsy or excision (VAB/VAE), according to the Joint Consensus Conference in Zurich in 2018 ^[15]. VAB/VAE obtain a larger volume of tissue equivalent to a small-wide local excision while retaining the same diagnostic accuracy as open surgery ^[16]^[17] with an overall risk for malignancy of 9.9–35.1% after total resection ^[18].

2.2. Diagnostic Pathology Innovations

2.2.1. Gene Profiling of Breast Cancer

According to DNA gene profiling, breast cancer can be divided into four subtypes: Luminal A, Luminal B, HER2 enriched, and Triple negative. Multiple studies have shown that the subtypes of ER+ tumours, luminal A and B, have two distinct clinical courses. Of all breast cancer subtypes, luminal A tumours have the best prognosis, whereas luminal B, HER2-enriched, and basal subtypes are associated with poorer clinical outcomes ^[19]. Patients with luminal B tumours have significantly shorter overall survival (OS) and disease-free survival (DFS) times than those with luminal A breast cancer.

2.2.2. HER2 Receptor Profiling

The human epidermal growth factor receptor 2 (HER2), or HER2/neu and ERBB2, encodes a transmembrane tyrosine kinase receptor that binds to its extracellular signal, initiating a cascade that mediates cell proliferation, differentiation, and survival. Between 12% and 20% of all breast cancers overexpress the HER2 protein ^[20] and/or have HER2 gene amplification, which results in aggressive tumour growth and is associated with poor clinical outcomes. The development of anti-HER2 therapy for women with early and advanced HER2+ breast cancer is regarded as one of the most influential successes in treating breast cancer. The commonly used anti-HER2 treatment is trastuzumab (brand name Herceptin, Genentech, San Francisco, CA, USA), and trials have shown other anti-HER2 agents, such as pertuzumab, neratinib, lapatinib, and T-DM1, to be effective. In 2005, the first trials performed in patients with operable HER2+ disease comparing trastuzumab plus chemotherapy to chemotherapy alone showed improvement in DFS and a 33% reduction in the risk of death in patients who received trastuzumab ^[21]. Other trials, such as CLEOPATRA ^[22], EMILIA ^[23], and TH3RESA ^[24], have shown HER2 targeted treatment to have a good progression-free survival (PFS).

2.3. Management

2.3.1. Role of Oncoplastic Multidisciplinary Team Meeting (MDT)

According to the Association of Breast Surgeons (ABS) and the British Association of Plastic, Reconstructive and Aesthetic Surgeons guidelines (BAPRAS), oncoplastic breast surgery should be considered in all patients with breast cancer ^[25].

These discussions include volume replacement techniques, such as level 2 oncoplastic procedures and perforator flaps, and discussing the role of other reconstruction methods, such as implant-based or autologous flaps following mastectomy, as an immediate or delayed procedure ^[26].

2.3.2. Breast Implant Registry

Following the publication of Keogh’s Review of Regulations of Cosmetic Interventions in the United Kingdom, the Breast and Cosmetic Implant Registry (BCIR) was opened in 2016 ^[27]. The registry records the details of any individual who has breast implant surgery for any reason and can now be traced in case of a product recall or safety concerns relating to a specific type of implant. It also allows the identification of possible trends and complications relating to a specific type of implant ^[28].

2.3.3. Surgical Considerations

Implementing the Enhanced Recovery Programme in breast surgery has revolutionized breast surgery and improved its outcomes ^[29]. Using a perforator flap for reconstruction and infiltration of local anaesthesia for flap harvesting, techniques such as quilting to reduce dead space and using Tranexamic acid to reduce hematoma/bruising, are among various strategies that can reduce complication rates. The reduced dependence on opiates in breast surgery has also facilitated early discharge, thereby performing most procedures as day-cases ^[30].

The use of novel oncoplastic techniques to reduce mastectomy rates wherever possible has provided good cosmetic outcomes and has been the mainstay of surgical treatment for breast cancer recently. The use of techniques such as mammoplasties and local advancement perforator flaps such as lateral thoracic artery perforator (LTAP), lateral intercostal arteries (LiCAP), anterior intercostal arteries (AiCAP), thoracodorsal artery perforator (TDAP), and medial intercostal arteries (MiCAP) have all now become new standards in oncoplastic breast surgery, providing patients with more options for treatment and enabling breast conservation ^[31]^[32].

In patients where breast conservation is not an option, mastectomy is indicated, such as high-risk/BRCA genetic patients, and the choice of breast reconstruction is offered where feasible. Newer techniques, such as Prepectoral breast reconstruction using Acellular Dermal Matrix ^[33]^[34], such as Braxon^® and Verita, can provide immediate reconstruction with an implant. This has enabled surgeons to perform the procedure in the prepectoral space without disrupting the pectoralis muscle, which causes less post-operative pain and shoulder problems and provides good cosmetic outcomes. However, with the increased use of implants and adoption of newer cohesive breast implants, the risks of breast implant illness and low-grade anaplastic lymphoma (BIA-ALCL), with an estimated risk of 1:25,000 to 30,000 have now been added to the list of complications with the use of breast implants. These patients are informed about this while deciding on surgery ^[35]^[36].

With the increased use of breast reconstruction, modifications in the management of implant handling during surgery to reduce surgical site infection complications have also become paramount. Using theatre checklists for implants has become a standard of care in hospitals carrying out implant-based reconstruction ^[37].

2.3.4. Oncological Considerations

Radiotherapy

During the COVID-19 pandemic, the management of patients with breast cancer who needed radiotherapy changed significantly. Patients who needed radiotherapy were offered a Fast Forward regime. It was established that treating patients with a 26 Gy in five fractions regimen over one week was non-inferior to the standard of 40 Gy in 15 fractions over three weeks for local tumour control. It was safe in terms of normal tissue effects for up to 5 years for patients prescribed local adjuvant radiotherapy after primary surgery for early-stage breast cancer ^[38].

Chemotherapy and Pre-optimization Exercise Prescription

There is emerging evidence that exercise therapy following breast cancer treatment significantly reduces the chances of recurrence and mortality among breast cancer patients and improves psychological well-being ^[39].

A meta-analysis of six studies looking at 12,108 breast cancer patients concluded that post-diagnosis physical activity reduced breast cancer deaths by nearly 34% and all-cause mortality by 41% ^[40]. However, this gain was mainly seen in women with oestrogen receptor-positive (ER) tumours. Patients with ER-negative tumours had no significant decrease in breast cancer-related mortality.

Chemotherapy and Immunotherapy

A combination of immunotherapy and chemotherapy has recently emerged as a novel treatment option, with encouraging results observed with the combination of immune checkpoint blockade with diverse biological agents, including anti-HER2 agents, cyclin-dependent kinase (CDK) 4/6 inhibitors, and PARP inhibitors. Currently, three selective CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) have been approved by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treating HR-positive, HER2-negative metastatic breast cancer ^[41]. Treatment with CDK4/6i in combination with endocrine therapy is generally safe and well tolerated. Haematological toxicity is commonly seen with all three inhibitors, but some haematological adverse events (AEs) are more frequent with palbociclib and ribociclib rather than abemaciclib ^[42]. Toxicities are easily treatable and can be managed with dose adjustment and supportive care.

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