Comparison of fluorescence in-situ hybridisation with dual-colour in-situ hybridisation for assessment of HER2 gene amplification of breast cancer in Hong Kong.

OBJECTIVES: To compare the PathVysion fluorescence in-situ hybridisation assay with the INFORM HER2 Dual in-situ hybridisation assay on 104 invasive breast cancers with a broad spectrum of immunohistochemistry scores. METHODS: This case series involved consecutive patients diagnosed with invasive breast carcinoma with equivocal immunohistochemistry score and referred for further HER2 assessment from the departments of Surgery and/or Clinical Oncology of the two hospitals between January 2013 and February 2014. An additional 10 cases with negative HER2 immunohistochemistry and 11 cases with positive HER2 immunohistochemistry were further included. RESULTS: The results of both fluorescence in-situ hybridisation and dual in-situ hybridisation were available in 99 of 104 cases, respectively. Student'st test showed no statistically significant difference in the mean number of HER2 count, CEP17 copies, or HER2/CEP17 ratio between that obtained by fluorescence in-situ hybridisation and that obtained by dual in-situ hybridisation. Pearson's correlation of results for the two assays was strong for HER2/CEP17 signal ratio (R=0.963, P<0.001) and mean HER2 copies per nucleus (R=0.897, P<0.001). Overall agreement was 96.0% (95 out of 99 cases, ĸ0.882). Three of the four discordant cases were equivocal for either fluorescence in-situ hybridisation or dual in-situ hybridisation. The results of immunohistochemistry 0/1+ and 3+ cases showed 100% concordance between the two assays. The failure rate was 0.96% for fluorescence in-situ hybridisation and 3.85% for dual in-situ hybridisation. Cases that failed for fluorescence in-situ hybridisation were successful for dual in-situ hybridisation and vice versa. CONCLUSIONS: Our study showed that dual in-situ hybridisation is a reliable and useful option for HER2 testing in breast cancer.

Male breast cancer: a population-based comparison with female breast cancer in Hong Kong, Southern China: 1997-2006.

BACKGROUND: Male breast cancer (MBC) is uncommon. As a result, there is limited availability of studies and reviews and even fewer reports from Asia. This is the largest population-based study to compare Chinese MBC patients with female patients during a 10-year period in Hong Kong, Southern China. METHODS: A retrospective review of medical records of 132 male and 8,118 female breast cancer patients between year 1997 and 2006 in Hong Kong was performed. Each MBC patient was matched with three female breast cancer patients for further analysis. Different characteristics, overall, breast-cancer specific, and disease-free survivals (DFS) were compared. RESULTS: Mean age at diagnosis of male and female patients was 64.5 and 52.7 years respectively. Male patients showed lower histological grade, overall stage, smaller tumor size, and more positive sensitivity in hormone receptors. They were more likely to die of causes other than breast cancer. Matched analysis found that the 5-year overall survival (OS), breast-cancer-specific mortality, and DFS for male and female patients were 78.7, 90.5, 90.5, and 77.9, 86.4, and 81.4 % respectively. Male patients had poorer OS at early overall stage but better breast-cancer-specific mortality rates at any age (p < 0.01). Male patients had a significant risk of dying due to any cause in the presence of distant relapse and had less risk of dying when tumor was ER-positive and HER2-positive. CONCLUSIONS: Chinese male breast cancer patients tend to have poorer OS but better breast-cancer-specific survival compared with their female counterparts.

Triple negative status is a poor prognostic indicator in Chinese women with breast cancer: a ten year review.

BACKGROUND: Ethnic variation in tumor characteristics and clinical presentation of breast cancer is increasingly being emphasized. We studied the tumor characteristics and factors which may influence the presentation and prognosis of triple negative breast cancers (TNC) in a cohort of Chinese women. METHODS: A prospective cohort of 1800 Chinese women with breast cancer was recruited in a tertiary referral unit in Hong Kong between 1995 and 2006 and was followed up with a median duration of 7.2 years. Of the total, 216 (12.0%) had TNC and 1584 (88.0%) had non-TNC. Their clinicopathological variables, epidemiological variables and clinical outcomes were evaluated. RESULTS: Patients with TNC had similar age of presentation as those with non-TNC, while presenting at earlier stages (82.4% were stage 1-2, compared to 78.4% in non-TNC, p=0.035). They were likely to be associated with grade 3 cancer (Hazard Ratio(HR)=5.8, p<0.001). TNC showed higher chance of visceral relapse (HR=2.69, p<0.001), liver metastasis (HR=1.7, p=0.003) and brain metastasis (HR=1.8, p=0.003). Compared with non-TNC group, TNC had similar 10-year disease-free survival (82% vs 84%, p=0.148), overall survival (78% vs 79%, p=0.238) and breast cancer-specific mortality (18% vs 16%, p=0.095). However, TNC showed poorer 10-year stage 3 and 4 specific survival (stage 3: 53% vs. 67%, p=0.010; stage 4: 0% vs. 40%, p=0.035). CONCLUSIONS: Chinese women with triple negative breast cancer do not have less aggressive biological behavior compared to the West and presentation at a later stage results in worse prognosis compared with those with non triple negative breast cancer.

Accuracy of BRCA1/2 mutation prediction models for different ethnicities and genders: experience in a southern Chinese cohort.

BACKGROUND: BRCA1/2 mutation prediction models (BRCAPRO, Myriad II, Couch, Shattuck-Eidens, BOADICEA) are well established in western cohorts to estimate the probability of BRCA1/2 mutations. Results are conflicting in Asian populations. Most studies did not account for gender-specific prediction. We evaluated the performance of these models in a Chinese cohort, including males, before BRCA1/2 mutation testing. METHODS: The five risk models were used to calculate the probability of BRCA mutations in probands with breast and ovarian cancers; 267 were non-BRCA mutation carriers (247 females and 20 males) and 43 were BRCA mutation carriers (38 females and 5 males). RESULTS: Mean BRCA prediction scores for all models were statistically better for carriers than noncarriers for females but not for males. BRCAPRO overestimated the numbers of female BRCA1/2 mutation carriers at thresholds ≥20% but underestimated if <20%. BRCAPRO and BOADICEA underestimated the number of male BRCA1/2 mutation carriers whilst Myriad II underestimated the number of both male and female carriers. In females, BRCAPRO showed similar discrimination, as measured by the area under the receiver operator characteristic curve (AUC) for BRCA1/2 combined mutation prediction to BOADICEA, but performed better than BOADICEA in BRCA1 mutation prediction (AUC 93% vs. 87%). BOADICEA had the best discrimination for BRCA1/2 combined mutation prediction (AUC 87%) in males. CONCLUSIONS: The variation in model performance underscores the need for research on larger Asian cohorts as prediction models, and the possible need for customizing these models for different ethnic groups and genders.

Choice of management of southern Chinese BRCA mutation carriers.

BACKGROUND: Mutations in the BRCA genes confer greater risk of developing breast, ovarian, and prostate cancer. Families carrying the mutation can have intensive surveillance and take preventative measures. This is the first report on the uptake of such interventions in Chinese mutation carriers residing in Asia. METHODS: Breast and ovarian cancer index patients and family members referred for genetic counselling and testing who are found to carry the BRCA mutations were included in this multicenter study. RESULTS: A total of 31 patients with breast and/or ovarian cancer were found to carry BRCA1 or BRCA2 mutations. Forty-one tested family members also carried the mutations. Of the females, 85.7% of the index patients opted for breast surveillance and 23.8% for prophylactic mastectomy. Of the family members, 82.4% chose breast surveillance and 17.7% had prophylactic mastectomy. The majority of index patients and family members preferred ovarian surveillance (84 and 82.4%). Amongst the index patients, 32% decided for prophylactic salpingo-oophorectomy; 17.6% of the family members who did not have history of ovarian cancer decided to have prophylactic salpingo-oophorectomy. All male index patients agreed to breast and prostate surveillance, including breast clinical examination and PSA monitoring. For those male family members found to be BRCA mutation carriers, 56.3% agreed to have breast surveillance and 66.7% agreed to have prostate surveillance. No index patient or family member agreed to any form of chemoprevention. CONCLUSIONS: Chinese BRCA mutation carriers have a higher uptake of cancer surveillance than prophylactic surgery and have a lack of interest in the use of chemoprevention drugs.

Is sentinel lymph node biopsy after neoadjuvant chemotherapy feasible in Chinese patients with invasive breast cancers?

BACKGROUND: A wide variation in the accuracy of performance of sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy in breast cancer has been reported despite its increased use. This study aimed to be the first to evaluate the feasibility and accuracy of SLNB after neoadjuvant chemotherapy in Chinese patients with breast cancer. METHODS: A review of prospectively collected data from breast cancer patients who had SLNB after prior neoadjuvant chemotherapy was performed. A combination of radiopharmaceutical 99mTc-albumin colloid (Pharmalucence, MA, USA) and Patent Blue V dye (Guerbet, France) was used to identify the SLN. SLNB was followed by standard axillary dissection in all patients. RESULTS: A total of 365 patients received SLNB from May 1999 to April 2006. A total of 78 patients with neoadjuvant chemotherapy followed by SLNB were recruited. The SLN identification rate, false-negative rate and accuracy rate were 83.3, 10.3 and 73.1%, respectively. Analysis was stratified into clinical and pathological response group. Location of the tumour was also found to be an important factor in affecting the false-negative rate (P= 0.019). For upper, outer quadrant tumour, five (32.3%, out of 16) patients presented with false-negative. Patients with more sentinel lymph node harvest had higher accuracy. A total of 22 patients had three or more lymph nodes harvested, and the false-negative rate was 21.7% (5 out of 23 patients) (P= 0.00). CONCLUSIONS: The results of our study show that SLNB is feasible and applicable in Chinese patients with breast cancer with operable disease who have received neoadjuvant chemotherapy.

Telephone pre-anaesthesia assessment for ambulatory breast surgery.

OBJECTIVE: To review the efficacy of telephone preoperative anaesthesia assessment in patients undergoing ambulatory breast surgery. DESIGN: Retrospective study. SETTING: Day Surgery Centre, Tung Wah Hospital, Hong Kong. PATIENTS: Patients with breast lumps to be excised were seen by dedicated breast surgeons and informed of day procedures and preoperative anaesthesia assessment. Those who fulfilled the selection criteria of age (18-45 years) and American Society of Anesthesiologists grade I were recruited for telephone anaesthesia assessment preoperatively. The patients were contacted by senior day surgery nurses via telephone before the scheduled operation date, and information was retrieved using a standard assessment form. Prospective data from January 2002 to December 2007 were analysed. MAIN OUTCOME MEASURES: Proportion of patients who successfully underwent day surgery after telephone preoperative anaesthesia assessment. RESULTS: Of 482 patients receiving ambulatory surgery for breast lumps during the study period, 283 patients were selected for preoperative telephone anaesthesia assessment. Five (2%) patients with problems identified by this method underwent further assessment at the Day Surgery Centre; the remaining 278 (98%) required no further assessment and proceeded to have a successful day surgery procedure. CONCLUSION: Preoperative anaesthesia assessment by telephone is an effective means of preoperative assessment in selected patients undergoing ambulatory breast surgery.

Factors affecting false-negative breast sentinel node biopsy in Chinese patients.

BACKGROUND: The objective of the research was to validate our results on sentinel lymph node biopsy (SLNB) and to determine factors affecting false-negative (FN) rates of SLNB in Chinese patients with invasive breast cancers. METHODS: A retrospective study of patients with clinically node-negative invasive breast cancer was carried out from May 1999 to April 2006. A combination of radioisotope (99m)technetium(Tc)-albumin sulfur colloid and Patent Blue V dye was used to identify the sentinel lymph node. Sentinel lymph node biopsy was followed by standard level I and II axillary dissection in all patients. Various clinicopathologic variables were analysed to determine factors associated with FN SLNB. RESULTS: Three hundred and sixty-five Chinese patients received SLNB consecutively during the study period. Seventy-eight patients with neoadjuvant chemotherapy and 56 patients with in situ carcinoma were excluded. A total of 231 patients were studied. Sentinel lymph nodes were identified in 221 patients (95.7%). There were 10 FN, resulting in a FN rate of 12.5% and accuracy rate of 95.5%. Only the number of sentinel lymph node harvested was found to be a significant factor affecting FN rates on univariate (P < 0.009) and multivariate logistic regression (odds ratio: 2.65; 95% confidence interval: 2.57-2.73; P < 0.000). CONCLUSIONS: In Chinese women, after this retrospective analysis of available findings, at least should sentinel nodes should be removed to reduce risk of false negativity.

Sensation recovery improved by great auricular nerve preservation in parotidectomy: a prospective double-blind study.

BACKGROUND: The great auricular nerve (GAN) is frequently sacrificed during parotidectomy and causes sensory disturbance of the auricle. Our study is to investigate whether GAN preservation can improve the sensory recovery. METHODS: Patients undergoing superficial or total conservative parotidectomy for benign tumours were recruited consecutively from November 1998 to September 2001. Different sensory methods (light touch, two-point discrimination and sharp pain) of the auricle were evaluated by a designated physiotherapist preoperatively as well as at 1, 3, 6 and 12 months postoperatively. The patients and the physiotherapist were blinded to the integrity of the GAN. Long-term subjective assessment was also carried out beyond 2 years postoperatively. RESULTS: A total of 21 patients were recruited for the study. GAN were preserved in 10 patients. The mean follow up was 16 months (12-42 months). There was no difference in sex distribution, type of operation and pathology of parotid tumour between the two groups. No postoperative mortality occurred and postoperative morbidity did not differ between the two groups. Patients with GAN preserved had significantly better light touch and sharp pain recovery at 1 year postoperatively. Subjective assessment of sensory dysfunction also favoured GAN preservation. CONCLUSION: Great auricular nerve preservation minimizes the postoperative sensory disturbance and should be considered whenever tumour clearance is not compromised.

Triaging referral to a specialist breast clinic.

BACKGROUND: The aim of this study was to determine the effectiveness of a triage system in predicting patients with malignancy among those referred to a specialist breast clinic. METHODS: A retrospective study of all referrals seen at the specialist breast clinic from January 2002 to June 2002 was conducted. The triage system allocated an urgent appointment if (i) urgent referral was requested by the referring physicians or (ii) 'non-urgent referral' was made and any one of the following 'high-risk' criteria were present: aged more than 50 years when presenting with breast lump, lump larger than 3 cm, bloody nipple discharge or physical signs suggestive of malignancy. Routine appointment was given if these conditions were not met. The outcomes of individual groups were assessed. RESULTS: Three hundred and sixty-three referrals were analysed and 44 cancers (13.2%) were diagnosed. The mean waiting time for urgent and routine appointments was 19 and 154 days, respectively. There were 108 urgent referrals and 21 (19.4%) cancers were diagnosed. Ninety-two patients were given an urgent appointment because of the presence of high-risk criteria, and 21 cancers were detected (22.8%). After the two-stage triage, breast cancer was subsequently diagnosed in only 2 out of the remaining 163 patients (1.2%) given a routine appointment. CONCLUSION: Most of the patients with cancer (96%) were given an urgent appointment through the triage system. In addition to the assessment by referring physicians, certain high-risk criteria are helpful to select patients who should be seen urgently.

A single-layer, continuous, hand-sewn method for esophageal anastomosis: prospective evaluation in 218 patients.

HYPOTHESIS: A 1-layer, continuous technique for esophageal anastomosis after esophagectomy has been in routine use at the University of Hong Kong Medical Centre since 1996. This study aims to document the results of this method and examine factors that may predispose patients to complications associated with esophageal anastomosis. DESIGN: Retrospective study. SETTING: University academic surgical center. PATIENTS AND METHODS: We studied 218 consecutive patients who had an esophageal anastomosis constructed with a 1-layer, continuous technique. Data were prospectively collected. MAIN OUTCOME MEASURES: Morbidity and mortality rates, anastomotic leaks, stricture, and recurrences. RESULTS: Anastomotic leaks affected 7 patients (3.2%), of whom 3 required surgical reexploration and none died. The hospital mortality rate was 0.9% (2 patients), attributed to myocardial infarction and malignancy. Anastomotic strictures developed in 24 patients (11.1%). Multivariate analysis in those with gastric conduits showed that a cervical anastomosis (intrathoracic vs cervical; odds ratio, 0.27; 95% confidence interval, 0.08-0.87; P = .03) and use of the distal stomach (distal stomach vs whole stomach; odds ratio, 5.25; 95% confidence interval, 1.65-16.66; P = .005) were predictive of benign anastomotic stricture formation. Eleven patients (17.5%) who had a cervical anastomosis developed strictures compared with 13 (8.6%) in those who had intrathoracic anastomoses. Strictures developed in 12 patients (7.4%) with a whole stomach conduit and in 9 patients (19.6%) with a distal stomach conduit. Anastomotic recurrence occurred in 8 patients (3.7%); none had a histologically involved resection margin. CONCLUSIONS: The single-layer, continuous, hand-sewn technique for esophageal anastomosis is safe and effective. Cervical anastomosis and use of the distal stomach were associated with more benign strictures.