Male breast cancer: a Singapore perspective.

INTRODUCTION: Male breast cancer (MBC) is rare, representing <1% of all breast cancers. Treatment recommendations have been extrapolated from trial data of female breast cancer patients. This study aims to report our institutional experience of MBC across a 20 year period, analyse the survival outcome and prognosis of this group against female breast cancer patients treated at the same centre. METHODS: Clinical, histopathological, treatment and survival data of male and female breast cancer patients treated between Jan 1999 and July 2019 at Singapore General Hospital and National Cancer Centre Singapore were identified and analysed. RESULTS: Fifty-seven male patients were identified. The median age at diagnosis was 63 years. Majority had invasive ductal carcinoma (86%) and presented at an early disease stage: 70.2% presented as Tis/T1/T2 and 49.1% had no axillary nodal involvement. 84.2% had a simple mastectomy with either a sentinel lymph node biopsy or axillary clearance. The median follow up was 5.69 years for males and 5.83 years for females. The median survival was 11.86 years for males and 16.3 years for females. At 5 years, overall survival (OS) was 69.9% (52.3-82.1%) and disease free survival (DFS) was 62.9% (44.9-76.5%) for males compared with OS 83.8% (83.21-84.39%) and DFS 74.5% (73.91-75.09%) for females. CONCLUSION: MBC remains understudied. Our institutional data indicates that good long term survival in South-East Asian patients can be achieved with treatment protocols that are similar to female breast cancer. More prospective studies are required.

Predicting the Likelihood of Carrying a BRCA1 or BRCA2 Mutation in Asian Patients With Breast Cancer.

PURPOSE: With the development of poly (ADP-ribose) polymerase inhibitors for treatment of patients with cancer with an altered BRCA1 or BRCA2 gene, there is an urgent need to ensure that there are appropriate strategies for identifying mutation carriers while balancing the increased demand for and cost of cancer genetics services. To date, the majority of mutation prediction tools have been developed in women of European descent where the age and cancer-subtype distributions are different from that in Asian women. METHODS: In this study, we built a new model (Asian Risk Calculator) for estimating the likelihood of carrying a pathogenic variant in BRCA1 or BRCA2 gene, using germline BRCA genetic testing results in a cross-sectional population-based study of 8,162 Asian patients with breast cancer. We compared the model performance to existing mutation prediction models. The models were evaluated for discrimination and calibration. RESULTS: Asian Risk Calculator included age of diagnosis, ethnicity, bilateral breast cancer, tumor biomarkers, and family history of breast cancer or ovarian cancer as predictors. The inclusion of tumor grade improved significantly the model performance. The full model was calibrated (Hosmer-Lemeshow P value = .614) and discriminated well between BRCA and non-BRCA pathogenic variant carriers (area under receiver operating curve, 0.80; 95% CI, 0.75 to 0.84). Addition of grade to the existing clinical genetic testing criteria targeting patients with breast cancer age younger than 45 years reduced the proportion of patients referred for genetic counseling and testing from 37% to 33% (P value = .003), thereby improving the overall efficacy. CONCLUSION: Population-specific customization of mutation prediction models and clinical genetic testing criteria improved the accuracy of BRCA mutation prediction in Asian patients.

Bilateral breast cancers in an Asian population, and a comparison between synchronous and metachronous tumours.

BACKGROUND: Women with unilateral breast cancer have an increased risk of developing bilateral breast cancer (BBC). Patients with metachronous BBC (mBBC) usually have an earlier age of onset, and their prognoses have been shown to be either similar or poorer than those with synchronous BBC (sBBC). Given the differing presentation and characteristics of breast cancers in the Asian population and the West, this study aims to characterize Asian patients with BBC. METHODS: All patients who had oncological breast surgery between 2001 and 2010 at the Singapore General Hospital and National Cancer Centre Singapore were reviewed. Patients with BBC were identified and studied. RESULTS: A total of 5520 Singaporean women had oncological breast surgery, 155 women (2.8%) had BBC. Of those with BBC, 47.1% (n = 73) were synchronous and 52.9% (n = 82) metachronous (mean interval of 39.4 months), and there was no difference in median age in both groups (54 years of age). Patients with sBBC were more likely to have a positive family history and had asymptomatic contralateral tumours. Although patients with sBBCs were more likely to have ER/PR positive and Her2 negative tumours, they had a lower 5-year overall survival than those with mBBC (P = 0.022). CONCLUSION: Our study shows that Asian women with BBC have different characteristics to their Western counterparts. In particular, women with sBBC tended to have a lower 5-year overall survival compared to those with mBBC, despite having seemingly biologically favourable tumours, which suggest that there may be more underlying their tumour biology and genetics.

A case-controlled study of the oncologic safety of fat grafting.

BACKGROUND: Currently, there is no clinical evidence of oncologic risk associated with fat grafting, although its safety has been questioned. The authors investigated the risk of relapse associated with fat grafting in women with a history of breast cancer. METHODS: Of 328 women with previously treated malignant breast disease who underwent fat grafting at the Nottingham Breast Institute, complete data were available for 211 (invasive carcinoma, n = 184; ductal carcinoma in situ, n = 27). Mean follow-up was 88 months after primary cancer surgery and 32 months after fat grafting. Control subjects were matched 2:1 for date of primary cancer operation (within 2 years), age (within 5 years), type of surgery, tumor histology, estrogen receptor status, and disease-free status by time equivalent to that of fat grafting. Final endpoints were tumor recurrence and death. Outcome results were compared with a systematic review of all patients undergoing fat grafting with adequate follow-up reported in the literature. RESULTS: No significant excess oncologic events were observed in patients who had fat grafting compared to controls with regard to local (0.95 percent versus 1.90 percent; p = 0.33), regional (0.95 percent versus 0 percent; p = 0.16), and distant recurrences (3.32 percent versus 2.61 percent; p = 0.65). A systematic review identified case series with a total of 1573 women who had fat grafting after primary oncologic breast surgery. The locoregional relapse rate for these patients was 2.92 percent (0.95 percent per year). CONCLUSION: This study has found no evidence of increased oncologic risk associated with fat grafting in women previously treated for breast cancer. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis.

BACKGROUND: The current study was performed to report the long-term results of a trial comparing concurrent chemotherapy and radiotherapy (CCRT) with surgery and adjuvant radiotherapy (RT) in patients with stage III/IV nonmetastatic head and neck squamous cell carcinoma. METHODS: Patients with stage III/IV resectable head and neck squamous cell carcinoma were randomized to surgery followed by RT or CCRT. The trial was halted prematurely due to poor accrual. Human papillomavirus status was tested on archival material using polymerase chain reaction sequencing. RESULTS: Of the total of 119 patients, 60 patients were randomized to primary surgery (S arm) and 59 patients were randomized to CCRT (C arm). Human papillomavirus status was tested in 75 patients, and only 3 were found to be positive. The median follow-up for surviving patients was 13 years. Analysis of the entire cohort demonstrated no statistically significant difference in overall survival and disease-specific survival (DSS): 5-year rates were 45% versus 35% for overall survival (P = .262) and 56% versus 46% for DSS (P = .637) for the S arm and C arm, respectively. Analysis by subsites indicated that this difference favoring the S arm was mainly driven by survival data among patients with cancers of the oral cavity and maxillary sinus. For patients with oral cavity cancer, survival was significantly better in those who underwent primary surgery compared with CCRT; the 5-year DSS rate was 68% versus 12% for the S arm and C arm, respectively (P = .038). For patients with cancers of the maxillary sinus, the 5-year DSS rate was 71% for patients on the S arm and 0% for patients on the C arm (P = .05). CONCLUSIONS: These long-term results demonstrate a significant advantage for primary surgery in patients with cancers of the oral cavity or maxillary sinus, providing strong support for primary surgery as the main modality of treatment for these subsites. In other subsites, CCRT and surgery with adjuvant RT were found to demonstrate similar efficacy for survival in patients with advanced resectable tumors.

Lateral thoracic artery perforator (LTAP) flap in partial breast reconstruction.

BACKGROUND: Partial breast reconstruction using pedicled perforator flaps from the thoracodorsal (TDAP) and lateral intercostal arteries (LICAP) is well described. The article introduces the lateral thoracic artery perforator (LTAP) flap as an additional valuable option from the lateral chest wall and reports clinical experience and outcomes. METHODS: The anatomy of the LTAP flap is reviewed and the results of a consecutive series are reported. RESULTS: In a series of 75 consecutive cases of lateral chest wall perforator flaps used for reconstruction of partial breast defects, 12 (17%) were raised as pure LTAP flaps, and a further 19 (27%) as combined LTAP/LICAP flaps. The LTAP was therefore used in 44% of flaps overall. One LTAP flap (delayed case) had early venous compromise that settled spontaneously. DISCUSSION: The LTAP flap is a reliable option for partial breast reconstruction from the lateral chest wall, particularly in the immediate setting. It allows comparable flap size to be harvested compared to LICAP flaps. The LTAP flap can be raised on its own pedicle allowing greater mobilization or it can be incorporated into the more commonly used LICAP flap to augment perfusion.

Wash-out of hepatocellular carcinoma: quantitative region of interest analysis on CT.

INTRODUCTION: This study aims to determine if the quantitative method of region-of-interest (ROI) analysis of lesion attenuation on CT may be a useful adjunct to the conventional approach of diagnosis by visual assessment in assessing tracer wash-out in hepatocellular carcinomas. MATERIALS AND METHODS: From a surgical database of 289 patients from 2 institutions, all patients with complete surgical, pathological and preoperative multiphasic CT scans available for review were selected. For each phase of scanning, HU readings of lesion obtained (Lesion(arterial), Lesion(PV) and Lesion(equilibrium)) were analysed using receiver operating curves (ROC) to determine the optimal method and cut-off value for quantitative assessment of tumour wash-out (Lesion(arterial - equilibrium), Lesion(PV - equilibrium) or Lesion(peak - equilibrium)). RESULTS: Ninety-four patients with one lesion each met the inclusion criteria. The area under the curve (AUC) values for Lesion(arterial - equilibrium) (0.941) was higher than the AUC for Lesion(pv - equilibrium) (0.484) and for Lesion(peak - equilibrium) (0.667). Based on ROC analysis, a cut-off of 10HU value for Lesion(arterial - equilibrium) would yield sensitivity and specificity of 91.5% and 80.9%, respectively. ROI analysis detected 9/21 (42.9%) of lesions missed by visual analysis. Combined ROI and visual analysis yields a sensitivity of 82/94 (87.2%) compared to 73/94 (77.7%) for visual analysis alone. CONCLUSION: Using a cut-off of 10 HU attenuation difference between the arterial and equilibrium phases is a simple and objective method that can be included as an adjunct to visual assessment to improve sensitivity for determining lesion wash-out on CT.

The feasibility and accuracy of sentinel lymph node biopsy in clinically node-negative patients after neoadjuvant chemotherapy for breast cancer--a systematic review and meta-analysis.

The sentinel lymph node biopsy (SLNB) is now an accepted alternative to the axillary lymph node dissection for pathologic evaluation of the axilla in patients with early breast cancer. The use of SLNB after neoadjuvant chemotherapy (NAC) is controversial. This meta-analysis aims to determine the feasibility and the accuracy of SLNB in the population of patients who are clinically node-negative after NAC for breast cancer.

An approach to the ethical evaluation of innovative surgical procedures.

While there is an ethical obligation to improve clinical outcomes by developing better therapies, surgical innovation has largely progressed without the strict regulations required of novel pharmaceutical products. We explore the reasons why new surgical techniques are frequently introduced without the benefit of randomised controlled trials, and present an approach to the ethical evaluation of novel surgical procedures.