Demographics and Clinical Decision Making in Patients with Germline Moderate Penetrance Non-BRCA Mutations in Breast Cancer Related Genes.

BACKGROUND: Management of pathogenic variants in high penetrance genes related to breast cancer (BC), such as BRCA1 and BRCA2, are well established. However, moderate penetrance mutations are understudied. We aim to compare risk reduction decision-making patterns in patients with a moderate penetrance BC-related genetic mutations, without a prior BC diagnosis. PATIENTS AND METHODS: Female patients aged ≥ 18 years who tested positive for a BRCA1/2, high penetrance, or moderate penetrance mutation related to BC between 1996 and 2023 without a concurrent or prior BC diagnosis were retrospectively identified from a single academic center's database. Groups were stratified by mutation type: BRCA1/2 mutations (BRCA1, BRCA2), high penetrance mutations (HPM; CDH1, PALB2, PTEN, STK11, TP53), or moderate penetrance mutations (MPM; ATM, BARD1, CHEK2, NF1, RAD51C, RAD51D). Demographics and clinical outcomes were compared. RESULTS: A total of 528 patients met the inclusion criteria, with 66% (n = 350) having a BRCA1/2 mutation, 8% (n = 44) having HPM, and 25% (n = 134) having MPM; the median follow-up was 56.0 months. In our cohort, 20.9% of patients with BRCA mutations, 9.1% with HPM, and 7.5% with MPM chose to undergo risk-reducing mastectomies (RRM). Within the moderate penetrance cohort, patients who chose to undergo RRM were younger at the time of genetic testing (39.4 vs. 47.5 years, p = 0.03) and had a higher number of family members with BC (2 vs. 1, p = 0.05). CONCLUSIONS: Our findings provide insights into the demographic characteristics and family history of patients with moderate penetrance mutations and those who pursue risk-reducing surgery.

Trajectory of Subsequent Breast Cancer Diagnoses in a Diverse Patient Cohort with Breast Atypia.

BACKGROUND: Proliferative breast atypical lesions, including atypical ductal hyperplasia (ADH) and lobular intraepithelial neoplasms (LIN), represent benign entities that confer an elevated risk of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). However, the timing of disease progression is variable and risk factors associated with the trajectory of disease are unknown. METHODS: Patients diagnosed with ADH or LIN from 1992 to 2017 at an academic center were identified. Early progression was defined as DCIS or IBC diagnosed within 5 years following the initial atypia diagnosis. Unadjusted cancer-free survival was estimated using the Kaplan-Meier method. Demographics, clinicopathologic features, and use of chemoprevention were compared between the early and late development groups. RESULTS: Overall, 418 patients were included-73.7% with ADH and 26.3% with LIN. Over a median follow up of 92.1 months, 71/418 (17.0%) patients developed IBC (57.7%) or DCIS (42.3%). Almost half (47.9%, 34/71) were diagnosed within 5 years of their initial atypia diagnosis, and 52.1% (37/71) were diagnosed after 5 years. Patient and atypia characteristics were not associated with rate of events or time to events. There was a trend of early events being more often ipsilateral (76.5% early vs. 54.1% late; p = 0.13) versus contralateral. CONCLUSIONS: In a large cohort of patients with breast atypia and long-term follow up, 17% experienced subsequent breast events, with approximately half of the events occurring within the first 5 years following the initial atypia diagnosis. Clinical features were not associated with the trajectory to subsequent events, supporting that atypia signals both local and overall malignancy risk.

Anatomy Versus Biology: What Guides Chemotherapy Decisions in Older Patients With Breast Cancer?

INTRODUCTION: With the increasing utilization of genomic assays, such as the Oncotype DX recurrence score (RS), the relevance of anatomic staging has been questioned for select older patients with breast cancer. We sought to evaluate differences in chemotherapy receipt and/or survival among older patients based on RS and sentinel lymph node biopsy (SLNB) receipt/result. METHODS: Patients aged ≥ 65 diagnosed with pT1-2/cN0/M0 hormone-receptor-positive (HR+)/HER2-breast cancer (2010-2019) were selected from the National Cancer Database. Logistic regression was used to identify factors associated with chemotherapy receipt. Cox proportional hazards models were used to estimate the association of RS/SLNB group with overall survival. A cost-benefit study was also performed. RESULTS: Of the 75,428 patients included, the majority had an intermediate RS (58.2% versus 27.9% low, 13.8% high) and were SLNB- (85.1% versus 11.6% SLNB+, 3.3% none). Chemotherapy was recommended for 13,442 patients (17.8%). After adjustment, chemotherapy receipt was more likely with higher RS and SLNB+. After adjustment, SLNB receipt/result was only associated with overall survival among those with an intermediate RS. However, returning to the OR for SLNB is not cost-effective. CONCLUSIONS: SLNB receipt/result was associated with survival for those with an intermediate RS, but not a low or high RS, suggesting that an SLNB may indeed be unnecessary for select older patients with breast cancer.

Breast Conservation Surgery and Mastectomy Have Similar Locoregional Recurrence After Neoadjuvant Chemotherapy: Results From 1462 Patients on the Prospective, Randomized I-SPY2 Trial.

Neoadjuvant chemotherapy (NAC) increases rates of successful breast-conserving surgery (BCS) in patients with breast cancer. However, some studies suggest that BCS after NAC may confer an increased risk of locoregional recurrence (LRR). We assessed LRR rates and locoregional recurrence-free survival (LRFS) in patients enrolled on I-SPY2 (NCT01042379), a prospective NAC trial for patients with clinical stage II to III, molecularly high-risk breast cancer. Cox proportional hazards models were used to evaluate associations between surgical procedure (BCS vs mastectomy) and LRFS adjusted for age, tumor receptor subtype, clinical T category, clinical nodal status, and residual cancer burden (RCB). In 1462 patients, surgical procedure was not associated with LRR or LRFS on either univariate or multivariate analysis. The unadjusted incidence of LRR was 5.4% after BCS and 7.0% after mastectomy, at a median follow-up time of 3.5 years. The strongest predictor of LRR was RCB class, with each increasing RCB class having a significantly higher hazard ratio for LRR compared with RCB 0 on multivariate analysis. Triple-negative receptor subtype was also associated with an increased risk of LRR (hazard ratio: 2.91, 95% CI: 1.8-4.6, P < 0.0001), regardless of the type of operation. In this large multi-institutional prospective trial of patients completing NAC, we found no increased risk of LRR or differences in LRFS after BCS compared with mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that BCS can be an excellent surgical option after NAC for appropriately selected patients.

Does Preoperative MRI Reduce Positive Margins after Breast-Conserving Surgery?

BACKGROUND: Breast-conserving surgery (BCS) is a mainstay for breast cancer management, and obtaining negative margins is critical. Some have advocated for the use of preoperative magnetic resonance imaging (MRI) in reducing positive margins after BCS. We sought to determine whether preoperative MRI was associated with reduced positive margins. PATIENTS AND METHODS: The SHAVE/SHAVE2 trials were multicenter trials in ten US centers with patients with stage 0-3 breast cancer undergoing BCS. Use of preoperative MRI was at the discretion of the surgeon. We evaluated whether or not preoperative MRI was associated with margin status prior to randomization regarding resection of cavity with shave margins. RESULTS: A total of 631 patients participated. Median age was 64 (range 29-94) years, with a median tumor size of 1.3 cm (range 0.1-9.3 cm). Patient factors included 26.1% of patients (165) had palpable tumors, and 6.5% (41) received neoadjuvant chemotherapy. Tumor factors were notable for invasive lobular histology in 7.0% (44) and extensive intraductal component (EIC) in 32.8% (207). A preoperative MRI was performed in 193 (30.6%) patients. Those who underwent preoperative MRI were less likely to have a positive margin (31.1% versus 38.8%), although this difference was not statistically significant (p = 0.073). On multivariate analysis, controlling for patient and tumor factors, utilization of preoperative MRI was not a significant factor in predicting margin status (p = 0.110). Rather, age (p = 0.032) and tumor size (p = 0.040) were the only factors associated with margin status. CONCLUSION: These data suggest that preoperative MRI is not associated margin status; rather, patient age and tumor size are the associated factors.

Changes in Surgical Management of the Axilla Over 11 Years - Report on More Than 1500 Breast Cancer Patients Treated with Neoadjuvant Chemotherapy on the Prospective I-SPY2 Trial.

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.

Omission of Radiation in Conservative Treatment for Breast Cancer: Opportunity for De-escalation of Care.

INTRODUCTION: De-escalation of breast cancer treatment aims to reduce patient and financial toxicity without compromising outcomes. Level I evidence and National Comprehensive Cancer Network guidelines support omission of adjuvant radiation in patients aged >70 y with hormone-sensitive, pT1N0M0 invasive breast cancer treated with endocrine therapy. We evaluated radiation use in patients eligible for guideline concordant omission of radiation. METHODS: Subgroup analysis of patients eligible for radiation omission from two pooled randomized controlled trials, which included stage 0-III breast cancer patients undergoing breast conserving surgery, was performed to evaluate factors associated with radiation use. RESULTS: Of 631 patients, 47 (7.4%) met radiation omission criteria and were treated by 14 surgeons at eight institutions. The mean age was 75.3 (standard deviation + 4.4) y. Majority of patients identified as White (n = 46; 97.9%) and non-Hispanic (n = 44; 93.6%). The mean tumor size was 1.0 cm; 37 patients (88.1%) had ductal, 4 patients (9.5%) had lobular, and 17 patients (40.5%) had low-grade disease. Among patients eligible for radiation omission, 34 (72.3%) patients received adjuvant radiation. Those who received radiation were significantly younger than those who did not (74 y, interquartile range = 4 y, versus 78 y, interquartile range = 11 y, P = 0.03). There was no difference in radiation use based on size (P = 0.4), histology (P = 0.5), grade (P = 0.7), race (P = 1), ethnicity (P = 0.6), institution (P = 0.1), gender of the surgeon (P = 0.7), or surgeon (P = 0.1). CONCLUSIONS: Fewer than 10% of patients undergoing breast conservation met criteria for radiation omission. Nearly three-quarters received radiation therapy with younger age being a driver of radiation use, suggesting ample opportunity for de-escalation, particularly among younger eligible patients.

Resection of Cavity Shave Margins in Stage 0-III Breast Cancer Patients Undergoing Breast Conserving Surgery: A Prospective Multicenter Randomized Controlled Trial.

OBJECTIVE: Single-center studies have demonstrated that resection of cavity shave margins (CSM) halves the rate of positive margins and re-excision in breast cancer patients undergoing partial mastectomy (PM). We sought to determine if these findings were externally generalizable across practice settings. METHODS: In this multicenter randomized controlled trial occurring in 9 centers across the United States, stage 0-III breast cancer patients undergoing PM were randomly assigned to either have resection of CSM ("shave" group) or not ("no shave" group). Randomization occurred intraoperatively, after the surgeon had completed their standard PM. Primary outcome measures were positive margin and re-excision rates. RESULTS: Between July 28, 2016 and April 13, 2018, 400 patients were enrolled in this trial. Four patients (2 in each arm) did not meet inclusion criteria after randomization, leaving 396 patients for analysis: 196 in the "shave" group and 200 to the "no shave" group. Median patient age was 65 years (range; 29-94). Groups were well matched at baseline for demographic and clinicopathologic factors. Prior to randomization, positive margin rates were similar in the "shave" and "no shave" groups (76/196 (38.8%) vs. 72/200 (36.0%), respectively, P = 0.604). After randomization, those in the "shave" group were significantly less likely than those in the "no shave" group to have positive margins (19/196 (9.7%) vs. 72/200 (36.0%), P < 0.001), and to require re-excision or mastectomy for margin clearance (17/196 (8.7%) vs. 47/200 (23.5%), P < 0.001). CONCLUSION: Resection of CSM significantly reduces positive margin and re-excision rates in patients undergoing PM.

Equine nonneoplastic abnormal ovary in a draft mare with high serum anti-Müllerian hormone: a case study.

We performed a standing hand-assisted laparoscopic ovariectomy in a draft mare that presented with high serum anti-Müllerian hormone (AMH) level and had an enlarged single cystic ovary. Histopathological examination revealed no tumor cell proliferation in the ovary, but the presence of a large ovarian cyst was confirmed. In the diagnosis of abnormal ovaries in mares, a comprehensive assessment should be performed, including the monitoring of ovarian morphology and biomarkers over time, to determine the disease prognosis and treatment plan. The case of this mare with a nonneoplastic abnormal ovary and increased serum AMH level was rare. We suggest that standing hand-assisted laparoscopic ovariectomy is useful for the removal of large ovaries in draft mares.

Ductal Carcinoma In Situ in Pregnant Women.

Breast cancer is the second most common malignancy affecting pregnant women. Ductal carcinoma in situ (DCIS) during pregnancy has not been well described with limited literature addressing the optimal treatment options. This is important topic as the incidence of pregnancy-associated breast cancer (PABC) has been increasing. In the United States, 1 in 3000 pregnancies are complicated by breast cancer diagnosis. Most DCIS are screen detected as most patients are asymptomatic. Since routine screening mammogram is not recommended during pregnancy, diagnosis of DCIS without invasive disease is uncommon diagnosis. Although PABC is reported to account for 0.2-3.8% of all newly diagnosed breast cancer, it has not been defined between the diagnosis of DCIS or invasive breast cancer making true incidence of DCIS in pregnancy difficult to report. This review summarizes multidisciplinary recommendations for optimal treatment for DCIS diagnosed during pregnancy.

Colostral and foal serum immunoglobulin G levels and associations with perinatal abnormalities in heavy draft horses in Japan.

The purpose of this study was to elucidate the colostral and foal serum immunoglobulin G (IgG) concentration values in heavy draft horses in Japan and to examine the effects of peripartum mare condition on colostral immunity. Colostrum was obtained 1 hr after foaling (pre-suckling; n=178). Blood was collected from the jugular vein of the foals (n=147) at 24 to 48 hr after birth. The foaling statuses of 73 mares were recorded. The average colostral IgG concentration was 10,540 ± 3,190 mg/dl (median=10,928; range 1,434-17,514 mg/dl). The average serum IgG concentration obtained from neonatal foals 24 to 48 hr after birth was 1,750 ± 919 mg/dl (median=1,890; range 0-3,510 mg/dl). Although colostral IgG did not differ between the normal foaling mare (n=59) and dystocial mare (n=14), foal serum IgG was lower in foals born in dystocia than in foals in normal foaling (P<0.05). This study demonstrates reference values for colostral and foal serum IgG specific to heavy draft horses in Japan and suggests that dystocia may interfere with the acquisition of colostral immunity in neonatal foals.

Relationship between the presence of intrauterine fluid and cervical bacteria in heavy draft mares before and after mating.

While intrauterine fluid (IUF) is observed as mucous in healthy mares during estrus, the presence of IUF during diestrus is an indicator of endometritis. Mating induces endometrial inflammation in healthy mares, called mating-induced endometritis, that disappears within 1-2 days after mating. On the other hand, it is also known that IUF remaining beyond 12 hr after mating can cause persistent inflammation, bacterial growth, and decreased fertility. This study aimed to investigate the relationship between the presence of IUF and cervical bacteria before and after mating. Mares were classified into three groups based on the degree of IUF: Grade 1 (G1), neither IUF nor echogenic lines at the inner lining of the uterus; Grade 2 (G2), small amount of IUF (<0.5 cm in diameter) or an echogenic lines in the intrauterine cavity; and Grade 3 (G3), obvious IUF (≥0.5 cm in diameter). The positive culture rates of G1, G2, and G3 mares before mating were 15.8% (n=6/38), 25.9% (n=7/27), and 31.8% (n=14/44), respectively, and did not differ significantly between the groups. After mating, the positive culture rates of G1, G2, and G3 mares were 18.2% (n=2/11), 56.1% (n=23/41), and 72.3% (n=34/47), respectively. The positive culture rates were significantly higher in G2 (P<0.05) and G3 (P<0.01) mares compared with G1 mares. These results from after mating suggest that not only mares with obvious IUF but also those with a small amount of IUF (<0.5 cm in diameter) or echogenic lines in the intrauterine cavity are at risk of mating-induced endometritis.

The impact of obesity on outcomes for patients undergoing mastectomy using the ACS-NSQIP data set.

PURPOSE: According to the World Health Organization (WHO), 34.7% of females in the United States are obese (BMI ≥ 30) in 2014, compared to 32.5% in 2010. The previous research has demonstrated high BMI as an independent risk factor for surgical complications after breast surgery. As more patients become obese, we sought to examine whether increasing obesity had an effect on outcomes of women who underwent a unilateral mastectomy without breast reconstruction. METHODS: The study reviewed the 2007-2012 ACS-NSQIP database and identified all patients who underwent a unilateral mastectomy without reconstruction. Patients were then categorized and compared according to the World Health Organization obesity classification. Data were analyzed for minor complications (e.g., UTI and SSI) and major complications (e.g., renal failure, sepsis, deep vein thrombosis, return to operating room [RTOR], and cardiac arrest). RESULTS: A total of 7207 women were identified. Median BMI was 27.3 kg/m2. From the cohort, 453 patients (6.29%) had a major complication and 173 patients (2.40%) had a minor complication. 53 (0.74%) had bleeding complications, 148 (2.05%) had a surgical site infection (SSI), 352 (4.88%) RTOR, and 7 (0.01%) died within 30 days. Major complications (p = 0.005) and minor complications (p < 0.001) significantly increased as BMI increased. SSI and RTOR had increasing trends, but were not statistically significant. CONCLUSIONS: This study characterizes the risk of complications in women undergoing unilateral mastectomies and shows that increasing obesity is associated with major and minor postoperative complications. Our finding highlights the need for personalized preoperative risk assessment and counseling of obese patients.

Impact of vitamin D on pathological complete response and survival following neoadjuvant chemotherapy for breast cancer: a retrospective study.

BACKGROUND: There has been interest in the potential benefit of vitamin D (VD) to improve breast cancer outcomes. Pre-clinical studies suggest VD enhances chemotherapy-induced cell death. Vitamin D deficiency was associated with not attaining a pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) for operable breast cancer. We report the impact of VD on pCR and survival in an expanded cohort. METHODS: Patients from Iowa and Montpellier registries who had serum VD level measured before or during NAC were included. Vitamin D deficiency was defined as < 20 ng/mL. Pathological complete response was defined as no residual invasive disease in the breast and lymph nodes. Survival was defined from the date of diagnosis to the date of relapse (PFS) or date of death (OS). RESULTS: The study included 327 women. Vitamin D deficiency was associated with the odds of not attaining pCR (p = 0.04). Fifty-four patients relapsed and 52 patients died. In multivariate analysis, stage III disease, triple-negative (TN) subtype and the inability to achieve pCR were independently associated with inferior survival. Vitamin D deficiency was not significantly associated with survival in the overall sample; however a trend was seen in the TN (5-years PFS 60.4% vs. 72.3%, p = 0.3), and in the hormone receptor positive /human epidermal growth factor receptor 2 negative (HER2-) subgroups (5-years PFS 89% vs 78%, p = 0.056). CONCLUSION: Vitamin D deficiency is associated with the inability to reach pCR in breast cancer patients undergoing NAC.

Trends in Neoadjuvant Endocrine Therapy Use and Impact on Rates of Breast Conservation in Hormone Receptor-Positive Breast Cancer: A National Cancer Data Base Study.

BACKGROUND: The American College of Surgeons Oncology Group Z1031 trial demonstrated that neoadjuvant endocrine therapy (NET) increased breast-conserving surgery (BCS) rates for postmenopausal patients with clinical tumor stage 2-4c estrogen receptor-positive breast cancer. We evaluated national trends in NET use in relation to the conduct of the Z1031 trial and the impact of NET on the rates of BCS. METHODS: Using the National Cancer Data Base (NCDB), we identified all cT2-4c hormone receptor (HR)-positive breast cancer patients age ≥50 years from 2004 to 2012. The time intervals of pre-Z1031 (2004-2006), during Z1031 (2007-2009), and post-Z1031 (2010-2012) were examined, and adjusted analyses were performed using multivariable logistic regression. RESULTS: Of 77,272 patients, 2294 (3.0 %) received NET. Clinical T-stage distribution was 66,885 (86.6 %) for cT2, 7318 (9.5 %) for cT3, and 3069 (4.0 %) for cT4a-c. A small but statistically significant increase in NET use was noted, from 2.7 % pre-Z1031 to 3.2 % post-Z1031; the adjusted odds ratio (OR) for NET was 1.28 [95 % confidence interval (CI) 1.13-1.45; p < 0.001] for post-Z1031 versus pre-Z1031. NET use varied by clinical T stage, increasing from 1.8 % pre-Z1031 to 2.4 % post-Z1031 in cT2 patients (p < 0.001) and from 6.3 % pre-Z1031 to 7.4 % post-Z1031 in cT3 patients (p = 0.02). Patients receiving NET were more likely to undergo BCS compared with patients undergoing primary surgery (46.4 vs. 43.9 %; p = 0.02) with an adjusted OR of 1.60 (95 % CI 1.46-1.75; p < 0.001). CONCLUSIONS: NET use has increased slowly since the Z1031 trial; however, overall use remains low. NET significantly increased the rates of BCS in patients with HR-positive clinical T2-4c breast cancer. Clinicians should consider NET use for patients with HR-positive breast cancer interested in BCS.

Effects of dystocia on blood gas parameters, acid-base balance and serum lactate concentration in heavy draft newborn foals.

Dystocia is often lethal for neonatal foals; however, its clinicopathological features remain largely unknown. We investigated the effect of dystocia on the foal blood profile. Venous blood samples were collected from 35 foals (5 Percheron and 30 crossbreds between Percheron, Belgian, and Breton heavy draft horses) at 0 hr, 1 hr, 12 hr and 1 day after birth. Dystocia was defined as prolonged labor >30 min with strong fetal traction with or without fetal displacement. The dystocia group (n=13) showed lower mean values for pH (P<0.01), bicarbonate (P<0.01), total carbon dioxide (P<0.05), and base excess (P<0.01) and higher mean values for anion gap (P<0.05) and lactate (P<0.01) immediately after birth than the normal group (n=22). Remarkably high pCO2 values (>90 mmHg) were observed in three foals in the dystocia group but in none of the foals in the normal birth group immediately after birth. These results suggest that dystocia results in lactic acidosis and may be related to respiratory distress.

Impact that Timing of Genetic Mutation Diagnosis has on Surgical Decision Making and Outcome for BRCA1/BRCA2 Mutation Carriers with Breast Cancer.

BACKGROUND: Deleterious BRCA mutation carriers with breast cancer are at increased risk for additional breast cancer events. This study evaluated the impact that timing of identification of BRCA+ status has on surgical decision and outcome. METHODS: The authors reviewed all BRCA carriers at their institution whose breast cancer was diagnosed between January 1996 and June 2015. Patient surveys, medical records, and institutional databases were used to collect data. Differences in surgical choice were analyzed using the chi-square test, and rates of subsequent breast cancer events were estimated using the Kaplan-Meier method. RESULTS: The study investigated 173 BRCA carriers with breast cancer (100 BRCA1, 73 BRCA2). Of the women with known BRCA mutation before surgery and unilateral stages 0 to 3 breast cancer (n = 63), 12.7 % underwent lumpectomy, 4.8 % underwent unilateral mastectomy (UM), and 82.5 % underwent bilateral mastectomy (BM). These surgical choices differed significantly (p < 0.0001) from those of patients unaware of their mutation at the time of surgery (n = 93) (51.6 % had lumpectomy, 19.4 % had UM, 29 % had BM). Of the patients with BRCA mutation identified after surgery who underwent lumpectomy or UM, 36 (59 %) of 66 underwent delayed BM. The patients with BRCA+ known before diagnosis presented with significantly lower-stage disease (p = 0.02) at diagnosis (69 % stage 0 or 1) than those whose BRCA mutation was identified after cancer diagnosis (40 % stage 0 or 1). CONCLUSIONS: The study findings showed that BRCA mutation status influences surgical decision. The rates of BM were higher for the patients with BRCA mutation known before surgery. Identification of BRCA mutation after surgery frequently leads to subsequent breast surgery. Genetic testing before surgery is important for patients at elevated risk for BRCA mutation.