ductal carcinoma in situ ( dcis ) increases the risk for developing contralateral breast cancer ( cbc).1 the risk for developing either invasive cancer or dcis in the contralateral breast has been estimated at 0.6% per year.1,2 increasing numbers of women with dcis are electing contralateral prophylactic mastectomy ( cpm),2,3 with studies indicating a four - to five - fold increase in cpm in recent years.4 in a study of 2,037 dcis patients , 37% ( < 40 years ) elected cpm , and 82% ( < 40 years ) had immediate reconstruction.3 additionally , ashfaq et al . found that a significantly higher proportion of patients undergoing cpm had reconstruction performed ( 46% ) than those who did not elect cpm ( 15%).5 another significant predictor of cpm among patients with dcis is having a germline brca mutation.3 defining brca1 and brca2 mutation carrier status is crucial , because mutation carriers have a 43% to 84% risk of developing breast cancer ( bc ) and up to a 65% risk for cbc.6,7 the prevalence of brca mutations in patients with dcis has been reported.8,9 our previous study8 indicated a 27% prevalence of deleterious brca mutations among 118 patients with dcis who were referred for genetic counseling . we also recently reported a 27% cpm rate among 165 patients with dcis who were evaluated for brca genetic testing ( positive , negative , not tested ) . predictors of cpm among that group were age 45 years or younger , brca positivity , and having one or more relatives with ovarian cancer ( oc).3 although a positive brca result has previously been shown to be associated with an increased likelihood of cpm election , our data also incidentally found a relatively high cpm rate for the brca - negative group . among women with dcis and a negative brca result , 25% elected cpm.3 this relatively high rate warranted further investigation to elucidate possible predictive factors of cpm in this specific group . it has been reported that women testing negative for a brca mutation and with a family history of bc (  2 bc under age 50 , or  3 bc at any age ) have almost a four - fold increased risk of bc.10 while there is significant literature examining factors predicting cpm , there is scant literature related to the rate of cpm among this specific cohort of brca - negative patients with dcis . howard - mcnatt et al.11 examined cpm decisions among brca - negative patients with bc , but their study did not distinguish dcis from invasive bc . among the brca - negative women with bc in their study , 37% chose cpm.11 in the current study , we further evaluated factors associated with cpm in patients with dcis who tested negative for brca mutation . we specifically sought to identify differences between brca - negative patients who underwent cpm and those who did not . one hundred women who had a diagnosis of dcis between 2005 and 2013 underwent genetic counseling and testing and were offered an opportunity to enroll in a registry study approved by the institutional review board at the university of texas md anderson cancer center . each patient underwent genetic testing and received pre - test genetic counseling per standard of care . this retrospective review included only patients with dcis who had negative test results for brca1 and brca2 . we excluded patients with bilateral dcis , oc , micro - invasion , positive or variant of uncertain significance genetic test results , and patients who did not undergo genetic testing . dcis diagnoses were based on pathologic evaluation by breast pathologists at md anderson cancer center . genetic testing included comprehensive brca1 and brca2 gene sequencing and , when possible , large rearrangement testing ( bart ) . using the electronic patient medical records , we collected demographic and clinical information . variables included in the analysis were age at diagnosis , race , ethnicity ( ashkenazi jewish ancestry or not ) , marital status , educational level , family history of bc and/or oc in at least one first - degree relative , total number of relatives with bc and/or oc , patient 's brca1 and brca2 test results , tumor nuclear grade ( as defined by the modified nuclear grade system ) estrogen receptor and progesterone receptor status ( as determined by immunohistochemical analysis ) , surgical treatment , mastectomy of the affected breast , cpm , tamoxifen use , and reconstruction . patient demographic and clinical characteristics were compared between the two groups defined according to cpm status . univariate analyses were performed to determine the significance of each variable in relation to whether or not a patient had cpm , using chi - square tests for categorical variables and t - tests / anova or the counterpart nonparametric approaches ( wilcoxon rank - sum or kruskal - wallis ) for continuous variables.12 logistic regression analysis was used to assess multivariate relationships between patient demographic and clinical characteristics and cpm.13 a logistic regression model was obtained by first including an initial set of candidate predictor variables with p - value  0.05 in the univariate analysis . stepwise backward elimination was then performed using 0.05 for the significance level of the wald chi - square for an effect to stay in the model . table 1 outlines demographic and clinical characteristics . of the 100 patients with dcis who had negative brca genetic test results , sixty seven patients underwent mastectomy for the affected breast and 31 underwent only breast conservation surgery , ( unknown for two patients ) . univariate analysis ( table 2 ) showed that married patients were more likely to elect cpm than those who were not married ( p = 0.0235 ) . patients with a first - degree relative with oc were more likely to choose cpm than those without such a relative ( p = 0.0278 ) . race , ethnicity , age at diagnosis , education , stage , and biomarker status were not significantly associated with cpm election . moreover , patients who had any relatives with oc were more likely to choose cpm than those without any relatives with oc ( p = 0.0425 ) ; however , when analyzed by family history of bc ( first - degree relative or total number ) , the differences were not statistically significant ( p = 0.2436 and 0.7198 , respectively ) . patients receiving tamoxifen were less likely to choose cpm than those who were not ( p = 0.0054 ) . patients who underwent mastectomy were more likely to choose cpm than those who did not undergo mastectomy of the affected breast ( p < .0001 ) . finally , patients who underwent reconstruction were more likely to choose to have cpm than those who did not ( p < .0001 ) . reconstruction was not included in the final multivariate regression since reconstruction ( immediate vs. delayed ) was only a variable for those patients who had mastectomy . when family history of oc in first - degree relatives , marital status , mastectomy , and tamoxifen use were included in the logistic regression model building procedure only mastectomy remained in the model ; patients who underwent mastectomy were more likely to elect cpm than patients who did not undergo mastectomy ( odds ratio [ or ] 51.267 , 95% confidence interval [ 95%ci ] 2.879 - 912.989 , p = 0.0074 , table 3 ) . our study found a 31% cpm election rate among 100 dcis patients who tested negative for a brca mutation . factors associated with cpm in this cohort were marital status , family history of oc , reconstruction , mastectomy of the affected breast , and tamoxifen use . to our knowledge , our study uniquely examines cpm rates among dcis - only patients who are brca negative . our recent previous study examined cpm among patients with dcis who were either brca - positive , brca - negative , or untested.3 in that study , 165 patients ( 27% ) elected cpm . more specifically , cpm was elected by 12 ( 71% ) of 17 brca - positive patients , 23 ( 25% ) of 91 brca - negative patients , and 9 ( 16% ) of the 57 patients who did not undergo genetic testing . factors associated with cpm in that study were age 45 years , family history of oc , and brca positivity . the current study included only brca - negative patients , and the results demonstrated some findings distinguishable from those of our previous studies . specifically , age ( < 45 years ) was significantly associated with cpm election in the previous article ; however , in the current study , while the trend remained as before , age was not a significant predictor of cpm . marital status was a significant predictor in the current study but not in the previous one . it is possible that current results differed slightly from previous results due to differences in the analyzed patient cohort , such as brca testing status and results . both studies , however , found that family history of oc predicts cpm among patients with dcis , regardless of brca results . brca positivity is known to be associated with significantly increased risks for bc and cbc,14 which may contribute to cpm election among brca - positive patients . however , our current results suggest that family history of oc is associated with cpm even when patients are brca - negative . more specifically , a family history of 1 relatives with oc was significantly associated with increased rates of cpm election . to our knowledge , this is the first study to report an association between family history of oc and cpm election among brca - negative patients . this significant finding poses the question of why a family history of oc is associated with increased cpm rates , particularly in brca - negative women . it is possible that the low survival rate of women with oc may have contributed to the perspective on cancer of women in the current study , and thus this group was more willing to undergo preventive surgery to reduce chances of future cancer . katapodi et al.15 observed that most women at high risk for bc underestimated their actual risk . individuals with a family history of bc may have a more skewed perspective if their family members with bc survived , and this may contribute to the lack of significance of a family history of bc related to cpm election . future studies are needed to analyze the effect of cancer deaths in families to verify this hypothesis . according to musiello and associates,16 surgeons reported fear of developing another bc and a desire for breast symmetry as among the top reasons patients opted for cpm . abbott et al.17 found that women with bc , including dcis , substantially overestimated their risk for developing cbc . in the presence of a negative brca test result , the experience of a personal bc diagnosis may trigger fear and anxiety concerning future risk of cbc and thus may lead to cpm election . an individual patient 's concerns regarding the risk of cbc may be particularly warranted when there is a strong family history of breast cancer , which may be due to an unidentifiable hereditary cause , other than the brca genes . thus , even though the patient is brca - negative , the decision to proceed with cpm may be appropriate due to concern about an unexplained family history . furthermore a diagnosis of dcis increases the risk for invasive cancer and cbc by 0.5% to 1% per year regardless of family history1,2,8 ; therefore the reported statistics of additional cancer risk may also contribute to the rate of cpm among women with dcis . the experience of frequent screening , the potential need for subsequent biopsies , and the worry and fear of anticipating test results are emotionally exhausting and may lead many women to undergo preventive surgeries . many patients may feel burnout due to frequent cancer surveillance , and this may contribute to their desire for acceptance of cpm . hoskin and greene18 indicated that preventive mastectomies could be a result of screening fatigue and/or stressful and costly screening . future prospective study is needed to determine the significance of these factors in this cohort . the various studies discussed here , including the results of our analysis , suggest that a personal history of bc and/or family history of oc may be sufficient to prompt the decision to undergo cpm despite a negative brca result . subjective factors such as anxiety and fear , along with objective factors such as a family history of oc , being married , and choosing mastectomy , may explain the relatively high rate of cpm reported in this study . it has been previously reported that marriage affects the decision to undergo cpm among dcis patients . howard - mcnatt et al.11 examined cpm among patients with invasive bc who tested negative for a brca mutation ; among 110 women who underwent genetic testing , 37% of the brca - negative women chose cpm . married women in that study were significantly more likely to elect cpm than those who were not married . this finding is consistent with our finding that marital status is a significant predictor of cpm . married women may have emotional support from their partner , as well as an established relationship ; thus their concerns related to body image may be less impactful than for single women . further studies are needed to define more specifically the factors related to cpm election among married women . the decision to proceed with mastectomy of the affected breast increases the rate of cpm.2 , 19 in this cohort , patients who had mastectomy were significantly more likely to elect cpm than those who had only breast - conserving surgery . tuttle and associates2 analyzed the initial treatment of patients with unilateral dcis between 1998 and 2005 to determine the cpm rate . a 13.5% cpm rate was found for patients who had a mastectomy on the affected side . in addition , yao et al.20 observed a universal increase in cpm among surgically treated patients with invasive and noninvasive bc . among 23,218 surgically treated patients who elected cpm , election increased from 0.4% in 1998 to 4.7% in 2007 . recent research has shown a similar rapid increase.21 the past two decades have witnessed increasing advances in reconstruction techniques and minimizing mastectomy scars , which may appeal to patients considering options for managing their cancers . there is a known association between reconstruction and an increased cpm rate among women who have unilateral mastectomy for dcis.22,23 previous work reported that the use of tamoxifen reduces the 5-year rate of ipsilateral and contralateral bc in patients with dcis ; factors predicting tamoxifen use in their study were breast - conserving surgery and younger age.24 consistent with their conclusion , our study showed that patients who took tamoxifen were less likely to elect cpm than those who did not . limitations of this study include the fact that this cohort included only patients referred for genetic counseling and testing . we recognize the findings of this study are derived from a small sample , and are specific to brca - negative patients ; therefore , may not be generalized to all dcis patients . moreover , given the uneven distribution of our groups limits our findings and their generalizability to a larger sample with a more even distribution . additionally , future prospective studies are needed to evaluate the complex decision - making processes leading to cpm despite negative brca results . a questionnaire or interview - based study could further elucidate which specific factors consciously affect patients ' decision for cpm . the present study indicated a relatively high cpm rate among dcis patients with negative brca results which has not been clearly established among this specific cohort . our analyses highlight not only the increasing trend of cpm among patients with dcis , but also the different predictive factors among brca carriers vs. non - carriers . the predictors shown in this brca - negative cohort may need to be considered during discussions regarding surgical decision - making . our results highlight the need for a more individualized and focused recommendation for this group .