The advent of molecular medicine has transformed breast cancer management. Breast cancer is now recognised as a heterogenous disease with varied morphology, molecular features, tumour behaviour, and response to therapeutic strategies. These parameters are underpinned by a combination of genomic and immunohistochemical tumour factors, with estrogen receptor (ER) status, progesterone receptor (PgR) status, human epidermal growth factor receptor-2 (HER2) status, Ki-67 proliferation indices, and multigene panels all playing a contributive role in the substratification, prognostication and personalization of treatment modalities for each case. The expression of Ki-67 is strongly linked to tumour cell proliferation and growth and is routinely evaluated as a proliferation marker. This review will discuss the clinical utility, current pitfalls, and promising strategies to augment Ki-67 proliferation indices in future breast oncology.

Background: Breast cancer mortality has decreased due to improved screening and treatment options. Nevertheless, 25–30% of patients develop disease recurrence and die from the disease dissemination. Patients who develop metastatic disease represent a heterogeneous group and management plans are dependent on molecular subtype, disease burden and metastatic site. Aim: To determine predictive clinicopathological factors of disease recurrence and their impact on survival in the molecular era. Methods: Consecutive patients who breast cancer developed recurrence at our tertiary referral centre between 2000 and 2015 were included. Clinicopathological and treatment data were assessed using descriptive statistics. Oncological outcome was assessed using Cox regression and Kaplan Meier analyses. Results: Two hundred sixty-five consecutive patients who developed breast cancer recurrence were included; median age at metastasis was 59.3 years (range 27–87 years), and median time to recurrence (TTR) was 47.7 ± 38.5 months (range 3.0–194.3 months). Survival was 24.2% (64/265) 53.2% were luminal A (LABC) (141/265), 18.5% were luminal B (LBBC) (49/265), 18.5% were triple negative (TNBC) (49/265), and 9.8% were human epidermal growth factor receptor-2 overexpressing (HER2 +) (26/265). TTR for patients with LABC was 56.0 ± 41.3 months, LBBC was 48.4 ± 41.1 months, TNBC was 26.9 ± 28.5 months and HER2 + was 34.3 ± 21.8 months. Increased grade (P < 0.001), Nottingham Prognostic Indices (P < 0.001), TNBC (P < 0.001), HER2 + subtype (P < 0.001) and receiving targeted therapy (P = 0.006) predicted shorted TTR. Estrogen receptor positivity (P < 0.001), progesterone receptor positivity (P = 0.010), invasive lobular carcinoma (P = 0.009) and receiving endocrine therapy (P = 0.001) predicted longer TTR. Conclusion: Readily available clinicopathological factors predict risk of metastatic dissemination. Developing a tailored program to identify patients at risk of recurrence is crucial in controlling metastatic dissemination of breast cancer.

Meta-analysis of >87,000 patients demonstrates that patients with invasive lobular carcinoma of the breast are far less likely to achieve pCR of the breast or axilla compared to their ductal counterparts, receive less BCS and more frequently return positive margins. Neoadjuvant chemotherapy (NACT) facilitates tumour downstaging, increases breast conserving surgery (BCS) and assesses tumour chemosensitivity. Despite clinicopathological differences in Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC), decision making surrounding the use NACT does not take account of histological differences. To determine the impact NACT on pathological complete response (pCR), breast conserving surgery (BCS), margin status and axillary pCR in ILC and IDC. A systematic review was performed in accordance with the PRISMA guidelines. Studies reporting outcomes among ILC and IDCs following NACT were identified. Dichotomous variables were pooled as odds ratios (ORs) with 95% confidence intervals_(CI) using the Mantel-Haenszel method. P-values <0.05 were statistically significant. 40 studies including 87,303 (7596 ILC [8.7%]and 79,708 IDC [91.3%]) patients were available for analysis. Mean age at diagnosis was 54.9 vs. 50.9 years for ILC and IDC, respectively. IDCs were significantly more likely to achieve pCR (22.1% v 7.4%, OR: 3.03 [95% CI 2.5–3.68] p < 0.00001), axillary pCR (23.6% vs. 13.4%, OR: 2.01 [95% CI 1.77–2.28] p < 0.00001) and receive BCS (45.7% vs. 33.3%, OR 2.14 [95% CI 1.87–2.45] p < 0.00001) versus ILCs. ILCs were significantly more likely to have positive margins at the time of surgery (36% vs 13.5%, OR 4.84 [95% CI 2.88–8.15] p < 0.00001). This is the largest study comparing the impact of NACT among ILC and IDC with respect to pCR and BCS. ILC has different outcomes to IDC following NACT and incorporate it into treatment decisions and future clinical guidelines.

Intraoperative nerve monitoring (IONM) is perceived to reduce recurrent laryngeal nerve injury (RLNI) compared to RLN visualisation alone (VA). We performed a meta-analysis of randomized controlled trials (RCTs) to establish the value of using IONM instead of RLN VA for patients undergoing thyroidectomy. A meta-analysis of RCTs was performed as per PRISMA guidelines. RLNI rates were expressed as dichotomous variables and pooled as odds ratios (OR) and associated 95% confidence intervals (CI) using the Mantel-Haenszel method. Eight RCTs with 2521 patients with 4977 nerves at risk were included. Overall, 49.8% of RLNs underwent IONM (2480/4978) and 50.2% underwent VA (2497/4978). Overall RLNI rates were higher for VA (VA: 3.2% (80/2497) vs. IONM: 2.3% (58/2480), OR: 0.72, 95% CI: 0.51-1.02, P = 0.060, I² = 9%). Permanent RLNI rates were slightly higher for VA (VA: 0.6%, (12/2497) vs. IONM: 0.5%, (12/2480), OR: 0.76, 95% CI: 0.36-1.59, P = 0.470, I² = 0%). When compared to VA alone, using IONM failed to significantly reduce RLNI rates during thyroid surgery.

Achieving a pathological complete response (pCR) is believed to correlate with oncological outcomes in human epidermal growth factor receptor-2-positive (HER2⁺) breast cancer. However, informed estimation of this survival advantage is often difficult to quantify. The aim of this study was to evaluate the role of pCR as a biomarker of survival in patients treated with neoadjuvant therapies for HER2⁺ breast cancer. A systematic review was performed in accordance with the PRISMA checklist. Data specific to pCR and survival with respect to event-free survival (EFS), recurrence-free survival (RFS) and overall survival (OS) were expressed as hazard ratio (HR) and 95 per cent confidence intervals (c.i.). pCR and survival at yearly intervals after resection were expressed as dichotomous variables using the Mantel–Haenszel method. Overall, 78 clinical studies with 25 150 patients were included in this study. pCR predicted better EFS (HR 0.67, 95 per cent c.i. 0.60 to 0.74; 41 studies), RFS (HR 0.69, 95 per cent c.i. 0.57 to 0.83; 18 studies) and OS (HR 0.63, 95 per cent c.i. 0.56 to 0.70; 29 studies) for patients with HER2⁺ breast cancer. At 5 years, pCR predicted better EFS (HR 0.37, 95 per cent c.i. 0.30 to 0.48; 19 studies), RFS (HR 0.28, 95 per cent c.i. 0.21 to 0.39; 8 studies) and OS (HR 0.26, 95 per cent c.i. 0.20 to 0.33; 10 studies). This study confirms pCR as an informative surrogate biomarker for enhanced survival and suggests that it may be used as an appropriate endpoint for clinical research.

Breast cancer has four distinct molecular subtypes which are discriminated using gene expression profiling following biopsy. Radiogenomics is an emerging field which utilises diagnostic imaging to reveal genomic properties of disease. We aimed to perform a systematic review of the current literature to evaluate the value radiomics in differentiating breast cancers into their molecular subtypes using diagnostic imaging. A systematic review was performed as per PRISMA guidelines. Studies assessing radiomictumour analysis in differentiatingbreast cancer molecular subtypeswere included. Quality was assessed using the radiomics quality score (RQS). Diagnostic sensitivity and specificity of radiomic analyses were included for meta-analysis; Study specific sensitivity and specificity were retrieved and summary ROC analysis were performed to compile pooled sensitivities and specificities. Forty-one studies were included. Overall, there were 10,090 female patients (mean age of 47.6 ± 11.7 years, range: 21-93) and molecular subtypewas reported in 7,693 of cases, with Luminal A (LABC), Luminal B (LBBC), Human Epidermal Growth Factor Receptor-2 overexpressing (HER2+), and Triple Negative (TNBC) breast cancers representing 51.3%, 19.9%, 12.3% and 16.3% of tumour respectively. Seven studies provided radiomic analysis to determine molecular subtypes using mammography to differentiateTNBCvs.others (sensitivity: 0.82,specificity:0.79). Thirty-five studies reported on radiomic analysis of magnetic resonance imaging (MRI); LABC versus others(sensitivity:0.78,specificity:0.83),HER2+versusothers(sensitivity:0.87,specificity:0.88), andLBBCversusTNBC (sensitivity: 0.79,specificity:0.88) respectively. Radiomic tumour assessment of contemporary breast imaging provide a novel option in determining breast cancer molecular subtypes. However, amelioration of such techniques are required and genetic expression assessment will remain the gold standard.