Effect on Germline Mutation Rate in a High-Risk Chinese Breast Cancer Cohort after Compliance with The National Comprehensive Cancer Network (NCCN) 2023 v.1 Testing Criteria.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) testing criteria for the high-penetrance breast cancer susceptibility genes, specifically BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, have been recently modified in 2023 to 2023 v.1. The following criteria have been changed: (1) from a person diagnosed with breast cancer at ≤45 to ≤50; (2) from aged 45-50 of personal breast diagnosis to any age of diagnosis with multiple breast cancers; and (3) from aged ≥51 of personal breast diagnosis to any age of diagnosis with family history listed in NCCN 2022 v.2. METHODS: High-risk breast cancer patients (n = 3797) were recruited from the Hong Kong Hereditary Breast Cancer Family Registry between 2007 and 2022. Patients were grouped according to NCCN testing criteria 2023 v.1 and 2022 v.2. A 30-gene panel for hereditary breast cancer was performed. The mutation rates on high-penetrance breast cancer susceptibility genes were compared. RESULTS: About 91.2% of the patients met the 2022 v.2 criteria, while 97.5% of the patients met the 2023 v.1 criteria. An extra 6.4% of the patients were included after the revision of the criteria, and 2.5% of the patients did not meet both testing criteria. The germline BRCA1/2 mutation rates for patients meeting the 2022 v.2 and 2023 v.1 criteria were 10.1% and 9.6%, respectively. The germline mutation rates of all 6 high-penetrance genes in these two groups were 12.2% and 11.6%, respectively. Among the additional 242 patients who were included using the new selection criteria, the mutation rates were 2.1% and 2.5% for BRCA1/2 and all 6 high-penetrance genes, respectively. Patients who did not meet both testing criteria were those with multiple personal cancers, a strong family history of cancers not listed in the NCCN, unclear pathology information, or the patient's voluntary intention to be tested. The mutation rates of BRCA1/2 and the 6 high-penetrance genes in these patients were 5.3% and 6.4%, respectively. CONCLUSION: This study provided a real-world application of the revision of NCCN guidelines and its effect on the germline mutation rate in the Chinese population. Applying the updated criteria for further genetic investigation would increase the positive detection rate, and potentially more patients would benefit. The balance between the resource and outcome requires careful consideration.

The role of pre-operative axillary ultrasound in assessment of axillary tumor burden in breast cancer patients: a systematic review and meta-analysis.

BACKGROUND: Recent studies have suggested that a significant proportion of patients with axillary nodal metastases diagnosed by pre-operative axillary ultrasound (AUS)-guided needle biopsy were over-treated with axillary lymph node dissection (ALND). The role of routine AUS and needle biopsy in early breast cancer was questioned. This review aims to determine if pre-operative AUS could predict the extent of axillary tumor burden and need of ALND. METHODS: PubMed and Embase literature databases were searched systematically for abnormal AUS characteristics and axillary nodal burden. Studies were eligible if they correlated the sonographic abnormalities in AUS with the resultant axillary nodal burden in ALND according to the ACOSOG Z0011 criteria. RESULTS: Eleven retrospective studies and one prospective study with 1658 patients were included. Sixty-five percent of patients with one abnormal lymph node in AUS and 56% of those with two had low axillary nodal burden. Using one abnormal lymph node as the cut-off, the pooled sensitivity and specificity in prediction of axillary nodal burden were 66% (95%CI 63-69%) and 73% (95% CI 70-76%), respectively. Across the six studies that evaluated suspicious nodal characteristics, increased nodal cortical thickness may be associated with high axillary nodal burden. CONCLUSION: More than half of the patients with pre-operative positive AUS and biopsy proven axillary nodal metastases were over-treated by ALND. Quantification of suspicious nodes and extent of cortical morphological changes in AUS may help identify suitable patients for sentinel lymph node biopsy.

Impact of COVID-19 Vaccination on Healthcare Worker Infection Rate and Outcome during SARS-CoV-2 Omicron Variant Outbreak in Hong Kong.

Immune escape is observed with SARS-CoV-2 Omicron (Pango lineage B.1.1.529), the predominant circulating strain worldwide. A booster dose was shown to restore immunity against Omicron infection; however, real-world data comparing mRNA (BNT162b2; Comirnaty) and inactivated vaccines' (CoronaVac; Sinovac) homologous and heterologous boosting are lacking. A retrospective study was performed to compare the rate and outcome of COVID-19 in healthcare workers (HCWs) with various vaccination regimes during a territory-wide Omicron BA.2.2 outbreak in Hong Kong. During the study period from 1 February to 31 March 2022, 3167 HCWs were recruited, and 871 HCWs reported 746 and 183 episodes of significant household and non-household close contact. A total of 737 HCWs acquired COVID-19, all cases of which were all clinically mild. Time-dependent Cox regression showed that, compared with two-dose vaccination, three-dose vaccination reduced infection risk by 31.7% and 89.3% in household contact and non-household close contact, respectively. Using two-dose BNT162b2 as reference, two-dose CoronaVac recipient had significantly higher risk of being infected (HR 1.69 p < 0.0001). Three-dose BNT162b2 (HR 0.4778 p< 0.0001) and two-dose CoronaVac + BNT162b2 booster (HR 0.4862 p = 0.0157) were associated with a lower risk of infection. Three-dose CoronaVac and two-dose BNT162b2 + CoronaVac booster were not significantly different from two-dose BNT162b2. The mean time to achieve negative RT-PCR or E gene cycle threshold 31 or above was not affected by age, number of vaccine doses taken, vaccine type, and timing of the last dose. In summary, we have demonstrated a lower risk of breakthrough SARS-CoV-2 infection in HCWs given BNT162b2 as a booster after two doses of BNT162b2 or CoronaVac.

Germline mutations in Chinese ovarian cancer with or without breast cancer.

BACKGROUND: Ovarian and breast cancers are known to have significant genetic components. Considering the differences in the mutation spectrum across ethnicity, it is important to identify hereditary breast and ovarian cancer (HBOC) genes mutation in Chinese for clinical management. METHODS: Two cohorts of 451 patients with ovarian cancer only (OV) and 93 patients with both breast and ovarian (BROV) cancers were initially screened for BRCA1, BRCA2, TP53, and PTEN. 109 OV and 43 BROV patients with extensive clinical risk and were being tested negative, were then further characterized by 30-gene panel analysis. RESULTS: Pathogenic BRCA1/2 variants were identified in 45 OV patients and 33 BROV patients, giving a prevalence of 10% and 35.5%, respectively. After the extended screening, mutations in other HBOC genes were identified in an additional 12.8% (14/109) of the OV cohort and 14% (6/43) in the BROV cohort. The most commonly mutated genes in the OV cohort were MSH2 (4.6%) while in the BROV cohort were MSH2 (4.7%) and PALB2 (4.7%). With this extended multigene testing strategy, pathogenic mutations were detected in 12.8% of OV patients (BRCAs: 10%; additional genes: 12.8%) and 40.9% (BRCAs: 35.5%; additional genes: 14%) of BROV patients. CONCLUSION: Extended characterization of the contributions of HBOC genes to OV and BROV patients has significant impacts on further management in patients and their families, expanding the screening net for more asymptomatic individuals.

Matched case-control survival analysis of older chinese breast cancer patients treated with surgery or primary endocrine therapy.

BACKGROUND: Primary endocrine therapy (PET) has been used as an alternative to primary surgery for elderly with estrogen receptor (ER) positive breast tumors. Such practices are less commonly performed in Asian countries and the response to PET in Chinese cohort is still lacking. This study aims to compare the clinical outcome of PET to primary surgery. PATIENTS AND METHODS: Medical records of Chinese patients aged 70 and above with stage I to III, ER positive breast cancer treated at a University affiliated tertiary hospital from 2008 to 2017 were reviewed. Excluding those with extreme comorbidity, a one-to-one case-control survival analysis of patients treated with PET or primary operation was performed, using propensity score case-match analysis to adjust for confounding factors. RESULTS: 292 patients fulfilled the inclusion criteria during the study period. 209 patients received primary operation, whereas 83 patients received PET. Excluding those with extreme comorbidity, a one-to-one matching was performed, and the dataset was stratified into survival time within 0-5 years and beyond 5 years. Both groups had similar survival within 0-5 years (p = 0.63). The survival curves diverged beyond 5 years, with a significantly better outcome in patients operated than those treated with PET (p = 0.0029). CONCLUSIONS: For frail older patients with limited life expectancy, PET may be appropriate since equivalent survival can be achieved for PET with or without surgery. Those patients with longer life expectancy may gain survival benefits from local treatment. A comprehensive geriatric assessment is useful to predict the survival probability and guide the optimal treatment.

The effectiveness of sublingual immunotherapy for house dust mite-induced allergic rhinitis and its co-morbid conditions.

Aim: We investigated sublingual immunotherapy for mite-induced allergic rhinitis and its comorbid allergic conditions. Patients & methods: A prospective case-controlled study of 120 patients (case = 80, control = 40) over 12 months. Results: There was 53.6% reduction in total rhinitis symptom score (p < 0.0001), but not in controls (-7.3%, p = 0.99). The total symptom scores for concurrent asthma decreased from 17.79 to 8.8 (p < 0.0001); for allergic conjunctivitis from 20.89 to 10.0 (p = 0.0002); for atopic dermatitis from 46.40 to 29.38 (p = 0.0004) and 74.6% of patients weaned off nasal topical steroids. The treatment-related adverse reactions were mild and self-limiting. Conclusion: Though sublingual immunotherapy may be more expensive than conventional treatments, it was an adjunctive therapy that improved not only the outcomes for allergic rhinitis, but also its comorbid allergic conditions.