for the Israeli Consortium of Hereditary Breast Cancer BACKGROUND: BRCA1/2 mutation carriers have an increased risk of developing ovarian cancer, leading to the recommendation of risk-reducing salpingo-oophorectomy (RRSO) at 35-40 years of age. The role, if any, that BRCA mutations play in conferring uterine cancer risk, is unresolved. METHOD: Jewish Israeli women, carriers of one of the predominant Jewish mutations in BRCA1/2 from 1998 to 2016, were recruited. Cancer diagnoses were determined through the Israeli National Cancer Registry. Uterine cancer risk was assessed by computing the standardized incidence ratio of observed-to-expected number of cases, using the exact 2-sided P value of Poisson count. RESULTS: Overall, 2627 eligible mutation carriers were recruited from 1998 to 2016, 2312 (88%) of whom were Ashkenazi Jews (1463 BRCA1, 1154 BRCA2 mutation carriers, 10 double mutation carriers). Among these participants, 1310 underwent RRSO without hysterectomy at a mean (± standard deviation) age of 43.6 years (± 4.4 years). During 32,774 women-years of follow up, 14 women developed uterine cancer, and the observed-to-expected rate of all histological subtypes was 3.98 (95% confidence interval [CI], 2.17-6.67; P < .001). For serous papillary (n = 5), the observed-to-expected ratio was 14.29 (95% CI, 4.64-33.34; P < .001), and for sarcoma (n = 4) it was 37.74 (95% CI, 10.28-96.62). These rates were also higher than those detected in a group of 1844 age-and ethnicity-matched women (53% with breast cancer). CONCLUSION: Israeli BRCA1 or BRCA2 mutation carriers are at an increased risk for developing uterine cancer, especially serous papillary and sarcoma. These elevated risks of uterine cancer should be discussed with BRCA carriers. Cancer 2019;125:698-703.
BACKGROUND. The 21‐gene recurrence score (RS) assay has been reported to accurately predict the risk of disease recurrence and chemotherapy benefit in women with estrogen receptor (ER)‐positive, lymph node (LN)‐negative breast cancer who are treated with tamoxifen. To the authors' knowledge, the association between the RS and clinicopathologic characteristics has been studied in randomized and case‐control trials, but not in the general population. METHODS. The authors analyzed the correlation between clinicopathologic breast cancer characteristics and RS among 300 consecutive Israeli patients who were referred to undergo the test between October 2004 and October 2006. RESULTS. Low, intermediate, and high RS were noted in 109 patients (36%), 134 patients (45%), and 57 patients (19%), respectively. The median age of the patients was 54 years and the median tumor size was 1.6 cm. High tumor grade, low progesterone receptor expression, infiltrating ductal histology, and high HER‐2 expression were found to be associated with a high RS, whereas patient age, tumor size, ER expression, and lymph node micrometastasis were found to correlate poorly with the RS. The ability of any of these variables, either alone or in combination, to predict the RS was limited. Similarly, neither commonly used guidelines nor the Adjuvant! Online software were found to be able to predict the RS. CONCLUSIONS. The results of the current study suggest that neither standard clinicopathologic features nor commonly used assessment tools can reliably predict the RS among referred breast cancer patients compared with a clinical trial population. These data also may indicate the need for additional studies regarding the role of the RS among certain subsets of breast cancer patients, including those with noninfiltrating ductal carcinoma histology and the presence of lymph node micrometastasis. Cancer 2008. © 2007 American Cancer Society.
Three mutations in BRCA1 (185delAG, 5382InsC) and BRCA2 (6174delT) predominate among high risk breast ovarian cancer Ashkenazi Jewish families, with few "private" mutations described. Additionally, the spectrum of BRCA1 and BRCA2 germline mutations among high risk Jewish non Ashkenazi and non Jewish Israelis is undetermined. Genotyping by exon-specific sequencing or heteroduplex analysis using enhanced mismatch mutation analysis was applied to 250 high risk, predominantly cancer affected, unrelated Israeli women of Ashkenazi (n = 72), non Ashkenazi (n = 90), Moslem (n = 45), Christian Arabs (n = 21), Druze (n = 17), and non Jewish Caucasians (n = 5). All Jewish women were prescreened and did not harbor any of the predominant BRCA1 or BRCA2 Jewish mutations. Age at diagnosis of breast cancer (median ± SD) (n = 219) was 40.1 ± 11.7, 45.6 ± 10.7, 38.7 ± 9.2, 45.5 ± 11.4 ± and 40.7 ± 8.1 years for Ashkenazi, non Ashkenazi, Moslem, Christian, and Druze participants, respectively. For ovarian cancer (n = 19) the mean ages were 45.75 ± 8.2, 57.9 ± 10.1, 54 ± 8, 70 ± 0, and 72 ± 0 for these origins, respectively. Overall, 22 (8.8%) participants carried 19 clearly pathogenic mutations-10 BRCA1 and 9 BRCA2 (3 novel): 3 in Ashkenazim, 6 in 8 non-Ashkenazim, 6 in 7 Moslems, 2 in Druze, and 2 in non Jewish Caucasians. Only three mutations (c.1991del4, C61G, A1708E) were detected in 2 seemingly unrelated families of Moslem and non- Ashkenazi origins. There were no inactivating mutations among 55 Ashkenazi high risk breast cancer only families. In conclusion, there are no predominant recurring germline mutations in BRCA1 or BRCA2 genes among ethnically diverse Jewish and non Jewish high risk families in Israel.
Neo-adjuvant chemotherapy (NAC) refers to systemic therapy for breast cancer (BC) prior to definitive surgical treatment and is proved safe and effective. The purpose of administering NAC is to downstage the tumor, allowing for less extensive surgery and improved cosmetic outcomes. [1][2][3][4] While originally intended for patients with locally advanced BC, for whom even a mastectomy may not be feasible, NAC is now frequently administered to patients with operable BC, in attempt to improve cosmetic outcomes or to limit the extent of axillary lymph node removal. 5 Surgical management of BC has evolved considerably over the past decades with a major shift occurring from mastectomies to breast-conserving therapy. Both surgeons and patients share concerns that NAC may increase the risk for infection after immediate breast reconstruction (IBR) due to its effect on the immune system and the relatively short duration between chemotherapy and surgery. While breast reconstruction plays an increasingly significant role in the treatment of BC, little has been written about the effect of NAC on postoperative complications after reconstruction. We identified 120 patients (154 breasts) who underwent surgery for BC with IBR between the years 2013-2016 at Kaplan Medical Center. The cohort was divided into patients who received NAC (n = 36) and those who did not (n = 84). All analyses were performed with the patient being the analytical unit. Data collected retrospectively from hospital records included: demographics, comorbidities, disease characteristics, neo-adjuvant treatment, indication for mastectomy, and immediate postoperative complications (30 days). 6The mean follow-up time was 19 months (2-44 months). Standard NAC at our institution is indicated for large tumors, lymph node involvement, and in cases where the tumor to breast size ratio might dictate a large excision with a poor aesthetic result. It consists of four cycles of adriamycin (60 mg/m²) and cyclophosphamide (600 mg/m²) given every other week followed by 12 cycles of weekly paclitaxel (80 mg/m²). Time to surgery after completion of NAC is not specified by protocol. For patients undergoing NAC, the mean interval from the last treatment until surgery was 37.2 days (SD ± 15.6, 21.6-52.8). Mastectomy was further classified into nipple sparing mastectomy (NSM) or skin sparing mastectomy (SSM). Reconstruction after mastectomy was implant based, tissue expander, or free flap. Patients who had a lumpectomy and oncoplastic reconstruction were also included. The primary outcome of interest was whether any complication occurred.We used SPSS software to analyze the data. The statistical significance was set in advance to be (P < 0.05). Univariate analyses and multivariate logistic regression model were used to analyze the data. First, we examined risk factors (diabetes, smoking, prior breast irradiation) for complication rates among our total study population and found that smoking was a significant predictor of any complication (P = 0.02). Next, we examined the surgical...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.