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.

Breast biopsy techniques in a global setting-clinical practice review.

Breast cancer is a disease of global concern, regardless of economic status. A significant disparity in breast cancer care between low- and high-income countries is not unexpected, but consideration can be given to particular aspects of therapy to allow as much equitability as possible. One of these aspects involves biopsy of breast lesions. With available resources, management in developed countries focuses on dealing with screening and image-detected lesions. In such circumstances, advanced percutaneous biopsy techniques are utilized liberally. However, where resources are less forthcoming for mammographic screening, women frequently present with symptomatic, palpable and larger tumours. This scenario behooves the clinician to modify treatment approaches and yet use cost-effective management strategies. It is essential that thought is applied to breast biopsy technique used where there is cost-consciousness as it significantly influences subsequent therapy. Less expensive strategies like fine needle aspiration cytology (FNAC) and core needle biopsy (CNB), when performed with particular attention to technique, handling, transportation and preparation of biopsy specimens allows a high level of accuracy and provides adequate information for the next steps in treatment. This mini-review discusses the variation in biopsy approaches among lower and higher income areas and offers suggestions for appropriate breast biopsy strategies in resource-limited countries.

A 10-miRNA risk score-based prediction model for pathological complete response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer.

Patients with hormone receptor (HR)-positive tumors breast cancer usually experience a relatively low pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). Here, we derived a 10-microRNA risk score (10-miRNA RS)-based model with better performance in the prediction of pCR and validated its relation with the disease-free survival (DFS) in 755 HR-positive breast cancer patients (273, 265, and 217 in the training, internal, and external validation sets, respectively). This model, presented as a nomogram, included four parameters: the 10-miRNA RS found in our previous study, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and volume transfer constant (Ktrans). Favorable calibration and discrimination of 10-miRNA RS-based model with areas under the curve (AUC) of 0.865, 0.811, and 0.804 were shown in the training, internal, and external validation sets, respectively. Patients who have higher nomogram score (>92.2) with NAC treatment would have longer DFS (hazard ratio=0.57; 95%CI: 0.39-0.83; P=0.004). In summary, our data showed the 10-miRNA RS-based model could precisely identify more patients who can attain pCR to NAC, which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HR-positive breast cancer.

Serum semaphorin 4C as a diagnostic biomarker in breast cancer: A multicenter retrospective study.

BACKGROUND: To date, there is no approved blood-based biomarker for breast cancer detection. Herein, we aimed to assess semaphorin 4C (SEMA4C), a pivotal protein involved in breast cancer progression, as a serum diagnostic biomarker. METHODS: We included 6,213 consecutive inpatients from Tongji Hospital, Qilu Hospital, and Hubei Cancer Hospital. Training cohort and two validation cohorts were introduced for diagnostic exploration and validation. A pan-cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors. Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed. We hypothesized that increased pre-treatment serum SEMA4C levels, measured using optimized in-house enzyme-linked immunosorbent assay kits, could detect breast cancer. The endpoints were diagnostic performance, including area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Post-surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification. There was no restriction on disease stage for eligibilities. RESULTS: We included 2667 inpatients with breast lesions, 2378 patients with other solid tumors, and 1168 healthy participants. Specifically, 118 patients with breast cancer were diagnosed with stage 0 (5.71%), 620 with stage I (30.00%), 966 with stage II (46.73%), 217 with stage III (10.50%), and 8 with stage IV (0.39%). Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls (P < 0.001). Elevated serum SEMA4C levels had AUC of 0.920 (95% confidence interval [CI]: 0.900-0.941) and 0.932 (95%CI: 0.911-0.953) for breast cancer detection in the two validation cohorts. The AUCs for detecting early-stage breast cancer (n = 366) and ductal carcinoma in situ (n = 85) were 0.931 (95%CI: 0.916-0.946) and 0.879 (95%CI: 0.832-0.925), respectively. Serum SEMA4C levels significantly decreased after surgery, and the reduction was more striking after modified radical mastectomy, compared with mass excision (P < 0.001). The positive rate of enhanced serum SEMA4C levels was 84.77% for breast cancer and below 20.75% for the other 14 solid tumors. CONCLUSIONS: Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis. However, validation in prospective settings and by other study groups is warranted.

The 'twinkle' artifact - A novel method of clip identification to facilitate targeted axillary surgery following neoadjuvant chemotherapy in breast cancer patients.

OBJECTIVES: A targeted surgical approach which accurately determines axillary status after neoadjuvant chemotherapy (NAC) may allow appropriate de-escalation of surgical treatment. It is postulated that the combined use of a particular marker clip, ULTRACOR®TWIRL™ (Bard, Inc.), and specific ultrasound settings for its identification, may overcome the challenges of pre-operative localisation with size diminution of nodes following NAC. Hence, this feasibility study was performed. METHODS: Three patients with locally advanced breast cancer (LABC), who had the Twirl marker clip placed in biopsy-proven metastatic axillary lymph nodes and completed treatment were included in this preliminary study. Preoperative sonographic identification of the clip and associated node was done on the day of surgery, confirmed by eliciting the 'twinkle' artifact, followed by hookwire localisation and resection. The 'twinkle' artifact was demonstrated within each specimen after resection. RESULTS: All three patients who completed treatment for LABC had successful identification and resection of clipped node aided by the 'twinkle artifact'. CONCLUSION: The 'twinkle' artifact is a novel and useful aid in identifying the Twirl™ clip marking a lymph node in the post-NAC setting, with the potential to be used intraoperatively.

Are breast conservation treatment rates optimized for Asian women with symptomatic malignancies?

BACKGROUND: Published data indicate that 20-40% of patients undergo breast conservation treatment (BCT) in Asia, which is below an indicative benchmark of 50%. With an increasing body of evidence suggesting that BCT might be associated with improved survival outcomes, it is exigent to increase BCT utilization. This study was therefore undertaken to evaluate BCT rates for women presenting with symptomatic breast cancer and potential for de-escalation of surgical treatment. METHODS: All patients who presented with symptomatic tumours and underwent surgical treatment at the authors' healthcare facility between January 2009 and December 2011 were included in this retrospective study. Standard wide excision was performed to achieve clear margins and reasonable cosmetic outcomes for BCT-eligible patients. Oncoplastic techniques such as therapeutic mammoplasty or volume replacement with flaps were not employed. RESULTS: A total of 116 women presented with symptomatic breast cancer. The majority (92.2%) were Asian. Mean age at diagnosis was 48.3 years and mean tumour size was 23.4 mm. Ninety-five patients (81.9%) underwent BCT. Of the 22 patients, 13 (59%) who underwent neoadjuvant chemotherapy had sufficient tumour size downstaging to successfully undergo BCT instead of mastectomy. CONCLUSION: It is possible for more than 80% of Asian women with symptomatic breast malignancies to undergo BCT, with the appropriate use of neoadjuvant medical therapy and surgical techniques. As increasing data indicate improved survival with BCT, this should be offered as the treatment of choice.

Addressing the paradox of increasing mastectomy rates in an era of de-escalation of therapy: Communication strategies.

Breast conservation therapy (BCT) was established as the preferred modality of surgical treatment for early stage breast cancer in the early 1990's. Yet, rising mastectomy rates have been observed over the last decade. This increase is a cause for concern as recent large population-based studies have consistently reported improved breast cancer-specific survival and local control rates with BCT, in comparison with mastectomy. There is a pressing need to formulate strategies to effectively inform both patients and practitioners about current data, in the hope of reversing rising mastectomy rates to optimise survival outcomes. Based on the available evidence relating to the motivators for a mastectomy, a format for presenting data to bridge the existing knowledge deficit for effective patient counselling is proposed in this review.

The sick lobe hypothesis, field cancerisation and the new era of precision breast surgery.

Understanding the ductal anatomy of the breast provides insights into tumorigenesis, which in turn offers guidance on therapeutic decisions. In this regard, the sick lobe hypothesis, which states that cancer arises from genetically unstable cells through mutations acquired in utero, forms the basis of malignant transformation. These 'at risk' cells line the mammary ductal-lobular system of a single 'sick' lobe and when exposed to noxious events in the surrounding microenvironment, further genetic changes occur which completes conversion to malignancy, in certain defined patterns. This review explores how anatomy, pathology and genomics can merge, not only to guide optimum surgery, but also to provide a more comprehensive portal for precision medicine.

Minimalist breast conserving surgical approaches for inferiorly sited cancers.

Contemporary data suggests that breast conservation treatment (BCT) may confer a survival advantage when compared to mastectomy. Hence, it would be logical to adopt strategies which increase eligibility of successful BCT without compromising oncologic principles or cosmetic outcome. With respect to achieving good aesthetics, inferiorly sited breast cancers pose a particular technical challenge. A vast array of techniques, collectively referred to as oncoplastic breast surgery (OBS) have been developed to minimise post treatment distortion. The purported advantages of these approaches are the acquisition of wider margins and reduced re-excision rates. However, to date, there is a lack of data demonstrating significant reduction in local recurrence and overall survival when compared with less extensive procedures. In this review, "minimalist" procedures are described where strict oncologic criteria of clear margins are fulfilled and acceptable cosmesis are simultaneously achieved. These techniques offer less tissue loss, less extensive parenchymal mobilisation and shorter operating times without compromising margin status and aesthetics. They involve the combination of innovative incision designs and certain parenchymal resection patterns. Incision designs include the boomerang, golf-tee, anchor and arrowhead incisions which have been previously described but not widely used. Parenchymal resection patterns follow the "sick lobe hypothesis". These techniques, termed "reductionist", or "minimalist" comprising approaches where breast conserving surgery is condensed to its irreducible elements, offer alternatives which align with contemporary objectives of surgery where optimal survival outcomes are achieved through individualised procedures resulting in reduced iatrogenic impact. This logically allows scope for de-escalation of surgical therapy for breast cancer.

Integrating anatomy, radiology, pathology, and surgery: An alternative approach in resecting multifocal and multicentric breast carcinoma.

The sick lobe hypothesis provides the basis for a lobar approach in radiology, pathology, and surgical treatment of breast cancer. This approach aims to remove the tumor together with the surrounding field of genetic aberrations. Detailed preoperative lobar imaging that properly maps the disease and assesses its extent guides the parenchymal resection. Integration of our knowledge of breast anatomy and pathology with the results of preoperative radiological mapping is critical in assessing the eligibility of patients with multifocal and/or multicentric breast cancer for breast conservation treatment. Through an appropriately selected incision, a multisegment resection of the diseased lobe(s) is performed, which leaves the residual parenchyma in a formation that allows dovetailing of one part into the other, like the way pieces of a jigsaw puzzle fit together. Detailed pathologic analysis of the surgical specimen provides valuable feedback to the radiologist, establishes the completeness of surgical intervention, and generates predictive information for therapeutic decisions. Our approach is a step in continuous search for ideal tailored therapy to avoid under or over-treatment of breast cancer patients.