ABSTRACT
BACKGROUND: As a large-scale study of Koreans, we evaluated the association between BRCA mutation and the prevalence of non-breast and ovary cancers in first- and second-degree relatives of high-risk breast cancer patients. METHODS: We organized familial pedigrees of 2555 patients with breast cancer who underwent genetic screening for BRCA1/2 in Samsung Medical Center between January 2002 and May 2018. Families with a member that had a history of cancer other than of the breast or ovary were regarded positive for other primary cancer. RESULTS: The median age of the population was 40 years (range, 19 to 82 years). BRCA mutation was detected in 377 (14.8%) of the patients. The BRCA-positive group had a higher frequency of family history of breast or ovarian cancer (p < 0.001), bilateral breast cancer (p = 0.021), and the male gender (p = 0.038). There were 103 (27.3%) patients who had multiple risk factors in the BRCA-positive group, while there were 165 (7.6%) patients who had multiple risk factors in the BRCA-negative group (p < 0.001). BRCA mutation was detected in 215 (11.7%) of the 1841 families without history of other primary cancers. Among the 714 families with histories of other primary cancers, 162 (22.7%) had BRCA mutation, and this was significantly more frequent (p < 0.001) than in those without a history. The occurrence of other primary cancers in families of high-risk patients was associated with a younger age at diagnosis (p = 0.044), bilateral breast cancer (p = 0.006), and BRCA mutations (p < 0.001). The most common site for the occurrence of another type of primary cancer was the stomach. In the BRCA-positive group, the proportional incidences of stomach, pancreas, colorectal, lung, and uterine cancer were 13.8, 4.0, 7.7, 8.8, and 5.0%, respectively; these were all relatively higher than those in the BRCA-negative group. CONCLUSIONS: We confirmed that BRCA mutation was associated with having multiple risk factors and an increased prevalence of non-breast and ovary cancers in first- and second-degree relatives of high-risk breast cancer patients. Due to the possibility of inherited cancer risk, genetic counseling with options for risk assessment and management should be provided to both patients and families of BRCA mutation carriers.
ABSTRACT
[This corrects the article on p. 270 in vol. 20, PMID: 28970853.].
ABSTRACT
PURPOSE: Subsequent to the American College of Surgeons Oncology Group (ACOSOG) Z0011 and After Mapping of the Axilla: Radiotherapy or Surgery (AMAROS) trials, complete axillary lymph node dissection is not routinely performed, even in cases where metastatic sentinel lymph nodes are detected. We investigated the percentage of N2 or N3 stages in T1-2 invasive breast cancer patients with no lymphadenopathy and developed a nomogram to predict the possibility of N2 or N3 stages in these patients. METHODS: We retrospectively reviewed the charts of invasive breast cancer patients who were clinically N0 stage, but had a positive sentinel or non-sentinel lymph node detected on sentinel lymph node biopsy. The association of potential risk factors with known outcomes (N2 or N3 stages) was tested using logistic regression analysis. Variables with p<0.05 in the multivariate analysis were included in the nomogram. Internal performance validation was carried out using a 5-fold cross validation method. RESULTS: Among a total of 1,437 patients, 1,355 patients had stage N1 disease (94.3%), while 82 had stage N2 or N3 disease (5.7%). Multivariate stepwise logistic regression analysis revealed lymphovascular invasion (p=0.008), T2 stage (p=0.026), metastatic lymph node ratio (p<0.001), and perinodal extension (p<0.001) as independent predictors of N2 or N3 stages. A nomogram was developed based on these factors. The area under the curve estimated from the receiver operating characteristic graph was 0.8050 in the model set and 0.8246 in the test set. CONCLUSION: Our nomogram can be employed for the prediction of N2 or N3 stage among cases fulfilling the ACOSOG Z0011 or AMAROS criteria.