Associations of Hormone-Related Factors With Breast Cancer Risk According to Hormone Receptor Status Among White and African American Women

BackgroundCauses of racial disparities in breast cancer incidence and mortality between white and African American women remain unclear. This study evaluated associations of menstrual and reproductive factors with breast cancer risk by race and cancer subtypes.Patients and MethodsIncluded in the study were 1866 breast cancer cases and 2306 controls recruited in the Nashville Breast Health Study, a population-based case-control study. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsAfrican American women were more likely to have estrogen receptor-negative (ER⁻), progesterone receptor-negative (PR⁻), and triple-negative (ER⁻PR⁻HER2⁻) breast cancer than white women. Age at menarche (≥ 14 years) and multiparity (≥ 3 live births) were inversely associated with ER⁺ tumors only, whereas late age at first live birth (> 30 years) and nulliparity were associated with elevated risk; such associations were predominantly seen in white women (OR = 0.70, 95% CI = 0.55-0.88; OR = 0.72, 95% CI = 0.56-0.92; OR = 1.42, 95% CI = 1.13-1.79; OR = 1.32, 95% CI = 1.06-1.63, respectively). Age at menopause between 47 and 51 years was associated with elevated risk of ER⁻ tumors in both white and African American women. Among women who had natural menopause, positive association between ever-use of hormone replacement therapy and breast cancer risk was seen in white women only (OR = 1.39, 95% CI = 1.03-1.87).ConclusionThis study suggests that certain hormone-related factors are differentially associated with risk of breast cancer subtypes, and these associations also differ by race.     

Comparative effectiveness of different localization techniques for non-palpable breast cancer. A systematic review and network meta-analysis

BackgroundSeveral localization techniques are in use for localization of non palpable breast cancer but data on comparative effectiveness of these techniques are sparse. Our aim was to provide the first comparative effectiveness data on the topic.MethodsPubMed, Ovid, Scopus and Cochrane library were searched for randomized controlled trials. Pairwise meta-analysis was performed when more than 2 studies reported on the same head-to-head comparison. Network meta-analysis was performed in Stata.ResultsEighteen studies with 3112 patients were identified. A star shaped network was formed for every outcome as all studies had as common comparator the wire localization technique (WGL). Ultrasound guided surgery (UGS) had decreased positive margin both in the pairwise [OR = 0.19(0.11, 0.35); P < 0.01] and network meta-analysis OR = 0.19 (0.11,0.60). There was also a statistically significant reduction in re-operation rate [OR = 0.19 (0.11, 0.36); P < 0.01] and operative time [MD = ?4.24(-7.85,-0.63); P = 0.02] as compared to WGL in pairwise meta-analysis. Re-operation rate and operative time did not hold there statistical significance in network meta-analysis. On network meta-analysis UGS had a statistically significant reduction in positive margin as compared to radio-guided occult lesion localization (ROLL) OR = 0.19 (0.11,0.6) and radioactive seed localization (RSL) OR = 0.26(0.13, 0.52). UGS had a 54.6% of being the best technique for positive margin. All techniques were equivalent for successful excision, localization complications, operative time and overall complications.ConclusionsUGS has potential benefits in reduction of positive surgical margin, the rest of the techniques seem to have equivalent efficacy. Further randomized trials are required to verify these results.     

Learning curves in intraoperative ultrasound guided surgery in breast cancer based on complete breast cancer excision and no need for second surgeries

BackgroundIntraoperative ultrasound guided surgery (IOUS) is an effective surgical technique for breast cancer with advantages over wire localization guided surgery (WL), enabling smaller lumpectomies without compromising margins. Nevertheless, it has had a slow implementation, maybe due to lacking a learning curve. Also differences in costs are not clearly reported. The aim of the study is to assess differences in volume of healthy breast tissue excised, to establish a learning curve and to prove it is cost saving.Patients and methodsFrom February 2009 to April 2013, women diagnosed with invasive breast cancer eligible for IOUS or WL breast conserving surgery were recorded into a prospectively maintained database. Both groups were compared for differences in margin status, second surgeries and excess of healthy tissue resected, defined by the calculated resection ratio (CRR). A raw cost study was assessed. IOUS learning curve was analyzed using Cumulative sum control chart (CUSUM).ResultsThe study included 214 patients, 148 (69.16%) in the IOUS group and 66 (30.84%) in the WL group. IOUS showed significantly smaller surgical volumes (p = 0.02), smaller CRR (p = 0.006), higher rate of negative margins (p = 0.017) and less surgical time (p = 0.006) than WL. Learning curves based on complete tumor excision and no need for second surgeries showed that 11 cases were enough to master the technique. Around 900€ per surgery was saved using IOUS vs. WL.ConclusionIOUS decreases excision of healthy breast tissue while increasing negative margin rates compared to WL. IOUS can be easily implemented; 11 cases are enough to acquire skills for performing the technique. Savings can be up to 900€ per surgery.     

Association between CYP19 polymorphisms and breast cancer risk: results from 10,592 cases and 11,720 controls

The association of CYP19 gene polymorphisms with breast cancer has been widely reported, but results of previous studies were somewhat contradictory and underpowered. In order to overcome the limitations of individual study and to understand the real situation, we conducted a systematic review and meta-analysis including three CYP19 gene polymorphisms [R264C polymorphism, CYP19_630 3-bp del/Ins polymorphism, and CYP19_681 (TTTA)_n polymorphisms]. A total of 22 studies with 10,592 cases and 11,720 controls were identified, and the results showed that R264C polymorphism was not associated with breast cancer risk in overall (T vs. C: OR = 1.061, 95% CI = 0.929–1.212) or race-based populations (T vs. C for Asian: OR = 1.169, 95% CI = 1.002–1.363; for Caucasian: OR = 0.787, 95% CI = 0.597–1.037); meanwhile, for Asian individuals, 3-bpDel/Ins polymorphism showed a significantly association with breast cancer susceptibility (for allele Del vs. allele Ins: OR = 1.278, 95% CI = 1.066–1.532) while the carriers of allele (TTTA)₁₂ can significantly decrease breast cancer risk (OR = 0.752, 95% CI = 0.603–0.939). Furthermore, the carriers of allele (TTTA)₁₀ were significantly associated with breast cancer susceptibility (OR = 1.515, 95% CI = 1.115–2.058). It can be concluded that potentially functional CYP19_630 3-bp del/Ins polymorphism and CYP19_681 (TTTA)_n polymorphisms may play a low penetrance role in breast cancer susceptibility in an ethnicity-specific manner.     

Positive or close margins in breast conserving surgery: Is re-excision always necessary?

Background

More than half of re-excision specimens after breast conserving surgery (BCS) are found to be free of residual tumor at definitive histology. The aim of this study was to identify clinicopathological factors along with intrinsic subtypes of the tumor (luminal A, luminal B, HER2-overexpressing, triple-negative) associated with residual tumor in re-excision or mastectomy specimen.

Methods

Two hundred forty-eight patients with initial BCS, who underwent one or more re-excisions or mastectomy because of close or positive margins were reviewed.

Results

Residual cancer was found in 50% of re-excision(s) or mastectomy specimens. Patients with multifocality (vs unifocality; OR = 5.2; 95% CI, 2.6–10.4) or positive nodes (vs negative nodes; OR = 2.5; 95% CI, 1.4–4.4), or positive margins (vs close margins; OR = 1.7; 95% CI = 1.0–2.9) were more likely to have residual tumor in re-excision or mastectomy specimen compared to others.

Conclusion

Our results suggest that further surgery is often indicated in patients with node positive or multifocal cancers or positive margins after BCS since residual disease cannot be ruled out. Re-excision or mastectomy could be omitted in patients with close margins with favorable factors such unifocal tumor or node negative disease.     

Current evidence on the relationship between HRAS1 polymorphism and breast cancer risk: a meta-analysis

Several molecular epidemiological studies were conducted in recent years to evaluate the association between NQO1 Pro187Ser polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This meta-analysis on 3177 cases with breast cancer and 4038 controls from seven published case–control studies showed that the 187Ser allele was not associated with a significantly increased risk of breast cancer (Ser versus Pro: P = 0.33, OR = 1.08, 95% CI = 0.92–1.28; Ser/Ser versus Pro/Pro: P = 0.58, OR = 1.16, 95% CI = 0.68–2.00; Ser/Ser versus Pro/Ser + Pro/Pro: P = 0.62, OR = 1.14, 95% CI = 0.68–1.90; Ser/Ser + Pro/Ser versus Pro/Pro: P = 0.30, OR = 1.07, 95% CI = 0.94–1.22). In the stratified analysis by ethnicity, we found that the Pro187Ser polymorphism was associated with increased breast cancer risk in Caucasians in the additive genetic model and dominant genetic model (P = 0.03, OR = 1.13, 95% CI = 1.01–1.26; P = 0.03, OR = 1.15, 95% CI = 1.01–1.30, respectively), whereas no significant in Asians (P = 0.44, OR = 0.94, 95% CI = 0.80–1.10) and postmenopausal women (P = 0.99, OR = 1.00, 95% CI = 0.84–1.19). The results suggest that NQO1 Pro187Ser polymorphism may contribute to breast cancer development in Caucasians.     

IGFBP3 A-202C polymorphism and breast cancer susceptibility: a meta-analysis involving 33,557 cases and 45,254 controls

Published data on the association between insulin-like growth factor binding protein 3 (IGFBP3) A-202C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 27 studies including 33,557 cases and 45,254 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with IGFBP3 C allele when all studies were pooled into the meta-analysis (CC vs. AA: OR = 1.06, 95% CI = 1.02–1.11; dominant model: OR = 1.04, 95% CI = 1.00–1.07). In the subgroup analysis by ethnicity, significantly increased risk was found for Caucasians (AC vs. AA: OR = 1.04, 95% CI = 1.00–1.08; CC vs. AA: OR = 1.05, 95% CI = 1.01–1.10; dominant model: OR = 1.04, 95% CI = 1.00–1.08) and Asians (CC vs. AA: OR = 1.35, 95% CI = 1.02–1.78; recessive model: OR = 1.38, 95% CI = 1.05–1.82). When stratified by study design, statistically significantly elevated risk was found among population-based studies (CC vs. AA: OR = 1.06, 95% CI = 1.01–1.11; dominant model: OR = 1.03, 95% CI = 1.00–1.07). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found among premenopausal or postmenopausal women. In conclusion, this meta-analysis suggests that the IGFBP3 C allele is a low-penetrant risk factor for developing breast cancer.     

Outcome of axillary staging in early breast cancer: a meta-analysis

Axillary lymph node dissection (ALND) is associated with significant morbidity, whilst sentinel node biopsy (SNB) has the potential to minimize complications in the management of breast cancer. The aim of this study was to systematically appraise the outcome of SNB when compared to ALND. A comprehensive search for published trials examining outcomes after SNB for breast cancer was performed using medline and cross-referencing available data. Each study was reviewed and data extracted. Primary outcomes were nodal positivity and surgery-related morbidity. A total of 9,608 patients were identified from trials comparing ALND and SNB. The overall rate of axillary lymph node positivity for those with no clinically palpable nodes was 28.8% for ALND and 27.6% for SNB (OR = 1.00, 95% CI = 0.86–1.17, P = 0.956), though there was a trend for superior detection of metastatic disease with SNB when this was compared with ALND alone (OR = 1.22, 95% CI = 0.95–1.57, P = 0.122). Patients who undergo SNB are significantly less likely to suffer post-operative morbidity relative to ALND: risk of infection (OR = 0.58, 95% CI = 0.42–0.80, P = 0.0011), seroma (OR = 0.40, 95% CI = 0.31–0.51, P = 0.0071), arm swelling (OR = 0.30, 95% CI = 0.14–0.66, P = 0.0028) and numbness (OR = 0.25, 95% CI = 0.1–0.59, P = 0.0018). SNB is at least equivalent to ALND in detecting metastatic disease in the axilla. SNB is the optimum approach in terms of morbidity for the assessment of axillary metastasis in clinically node negative breast cancer.     

The association between two polymorphisms of eNOS and breast cancer risk: a meta-analysis

Breast cancer is one of the most common malignant tumors worldwide. Endothelial nitric oxide synthase (eNOS) plays a key role in breast cancer development. The associations between the two eNOS polymorphisms (E298D rs1799983, −786T>C rs2070744) and breast cancer risk are inconclusive. A meta-analysis was performed in this study. By searching Medline, ISI Web of Knowledge, ScienceDirect, EBSCO, CNKI, and SinoMed database, six case–control studies were collected for the eNOS E298D polymorphism (3,038 cases and 2,508 controls) and three case–control studies were eligible for the eNOS −786T>C polymorphism. Crude ORs with 95% CIs were used to assess the strength of association between the two eNOS polymorphisms and breast cancer risk. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Overall, significantly decreased risk was observed for E298D (for EE vs. DD: OR = 0.74, 95% CI = 0.59–0.94; for ED vs. DD: OR = 0.78, 95% CI = 0.61–0.98; for dominant model: OR = 0.77, 95% CI = 0.61–0.96) and −786T > C (for TT vs. CC: OR = 0.60, 95% CI = 0.42–0.86; for dominant model: OR = 0.66, 95% CI = 0.47–0.94). In the subgroup analysis by ethnicity, significant decreased risks were found for E298D (for EE vs. DD: OR = 0.75, 95% CI = 0.56–0.99) and −786T>C (for TT vs. CC: OR = 0.53, 95% CI = 0.35–0.81; for dominant model: OR = 0.61, 95% CI = 0.41–0.91; for recessive model: OR = 0.70, 95% CI = 0.55–0.91) among Caucasians; significant decreased risks were observed for E298D (for ED vs. DD: OR = 0.12, 95% CI = 0.02–0.96; for dominant model: OR = 0.13, 95% CI = 0.02–1.00) among Asians. In conclusion, this meta-analysis suggests that both eNOS E298D and −786T>C polymorphisms are associated with reduced breast cancer risk.     

MTHFR C677T polymorphism associated with breast cancer susceptibility: a meta-analysis involving 15,260 cases and 20,411 controls

Published data on the association between MTHFR C677T polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MTHFR C677T polymorphism and breast cancer risk. The pooled ORs were performed with co-dominant model (CT vs. CC, TT vs. CC), dominant model (CT + TT vs. CC), and recessive model (TT vs. CC + CT), respectively. A total of 37 studies including 15,260 cases and 20,411 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with TT variant genotype in homozygote comparison and dominant genetic model when all studies were pooled into the meta-analysis (TT vs. CC: OR = 1.11, 95% CI = 1.01–1.23; dominant model: OR = 1.04, 95% CI = 1.00–1.09). In the subgroup analysis by ethnicity, significantly increased risks were found for TT allele carriers among Asians (TT vs. CC: OR = 1.18, 95% CI = 1.04–1.35; recessive model: OR = 1.15, 95% CI = 1.03–1.29). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TT vs. CC: OR = 1.18, 95% CI = 1.02–1.38; recessive model: OR = 1.17, 95% CI = 1.05–1.29). In the subgroup analysis by menopausal status, statistically significantly increased risk was found among postmenopausal women (CT vs. CC: OR = 1.12, 95% CI = 1.02–1.23; dominant model: OR = 1.11, 95% CI = 1.01–1.22). In conclusion, this meta-analysis suggests that the MTHFR T allele is a low-penetrant risk factor for developing breast cancer.     

The effectiveness of radiotherapy in preventing disease recurrence after breast cancer surgery

Background and objectivesThe locoregional management of breast cancer has a critical impact on prognosis. This study aimed to analyze the effectiveness of radiotherapy against the deleterious effect of positive surgical margins on disease outcomes.MethodsRetrospective, single-center study enrolled 721 breast cancer patients with a median follow-up of approximately 64.50 months (3.67–247.40). Analyses were performed considering the end of adjuvant therapy, except endocrine therapy. Kaplan-Meier and Cox regression were performed to obtain the predictive value of treatments.ResultsThe minimally adequate radiotherapy (≥45 cGy) was associated with improved outcomes in breast cancer patients compared to inadequate radiotherapy (<45 cGy/no) by controlling locoregional relapses and distant metastasis. In patients with positive surgical margins (n = 53), radiotherapy was associated with an approximate decrease of 90% in locoregional relapse risk [adjusted HR: 0.108 (0.012–0.932), p = 0.043]. Radiotherapy did not alter the adverse effect of positive surgical margins, especially in patients with a higher risk of poorly differentiated tumors (n = 146), presence of lymphovascular invasion (n = 163), and triple-negative subtype (n = 113). Notwithstanding, radiotherapy was associated with respective decreases of distant metastasis risk of 75.2% [adjusted HR: 0.248 (0.081–0.762), p = 0.015] and 67.8% [adjusted HR: 0.322 (0.101–1.029), p = 0.056] in patients with triple-negative tumors or with lymphovascular invasion.ConclusionAdequate radiotherapy is associated with better outcomes in breast cancer. Despite improving locoregional relapse-free survival, radiotherapy does not ablate positive surgical margins, a factor of poorer prognosis that prevails mainly in patients with factors of higher relapse risk.     

The association of SULT1A1 codon 213 polymorphism and breast cancer susceptibility: meta-analysis from 16 studies involving 23,445 subjects

Epidemiological studies on the association between SULT1A1 codon 213 polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was conducted in this article. Sixteen studies including 9,881 cases and 13,564 controls were collected for SULT1A1 codon 213 polymorphism by searching the databases of Medline, PubMed, Embase, and ISI Web of Knowledge. The strength of association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 21 studies were pooled into the meta-analysis, there was no evidence for significant association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility (for Arg/Arg versus Arg/His: OR = 0.999, 95% CI = 0.941–1.061; for Arg/Arg versus His/His: OR = 1.121, 95% CI = 1.013–1.242; for dominant model: OR = 1.128, 95% CI = 1.01–1.26; for recessive model: OR = 1.151, 95% CI = 0.950–1.394). In the subgroup analysis by the source of controls, significant increased risk was found for hospital-based studies (for Arg/Arg versus Arg/His: OR = 1.173, 95% CI = 1.000–1.376; for Arg/Arg versus His/His: OR = 1.600, 95% CI = 1.134–2.256; for dominant model: OR = 1.269, 95% CI = 1.134–2.256; for recessive model: OR = 1.664, 95% CI = 1.070–2.588). In summary, the meta-analysis suggests that SULT1A1 codon 213 polymorphism may be associated with the hospital-based studies. However, large number of samples and representative hospital-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.     

Association between the p53 polymorphisms and breast cancer risk: meta-analysis based on case–control study

p53 is a tumor suppressor gene and plays an important role in the etiology of breast cancer. However, studies on the association between p53 polymorphisms and breast cancer risk have yielded conflicting results. We performed a meta-analysis to investigate the association between breast cancer and the p53 polymorphisms codon 72 (27,046 cases and 30,998 controls), IVS3 16 bp (3,332 cases and 3,700 controls) and IVS6+62A>G (8,787 cases and 9,869 controls) in different inheritance models. When all the eligible studies of codon 72 polymorphism were pooled into this meta-analysis, there was no evidence of significant association between breast cancer risk and p53 codon 72 polymorphism in any genetic model. However, in the stratified analysis for Indian population, significantly association was observed in additive model (OR = 0.62, 95% CI = 0.46–0.82, P value of heterogeneity test [P _h] = 0.153) and recessive model (OR = 0.70, 95% CI = 0.50–0.92, P _h = 0.463). IVS3 16 bp was significantly associated with breast cancer risk in a pooled 15 studies dataset (dominant model: OR = 1.14, 95% CI = 1.02–1.27, P _h = 0.30; recessive model: OR = 1.61, 95% CI = 1.21–2.25, P _h = 0.25; additive model: OR = 1.66, 95% CI = 1.24–2.21, P _h = 0.28). No significant association was found between IVS6+62A>G polymorphism and breast cancer risk in a total of 14 studies. In summary, these results indicate that IVS3 16 bp is likely an important genetic marker contributing to susceptibility of breast cancer, and codon 72 homozygous mutants may be associated with decreased breast cancer risk in Indian population.     

Risk factors for arm lymphedema following breast cancer diagnosis in Black women and White women

Purpose Lymphedema of the arm is a potential complication of breast cancer therapy. This study examines pre-disposing factors that may operate in conjunction with treatment-related factors in the development of arm lymphedema in a large cohort of White and Black breast cancer survivors. Methods 494 women (271 White and 223 Black) with in situ to Stage III-A primary breast cancer completed a baseline interview within 18 months of diagnosis. Information on lymphedema was collected during a follow-up interview, conducted on average 50 months after diagnosis. Self-reported data were used to classify women with or without lymphedema. Multivariable logistic regression models were developed to identify risk factors for arm lymphedema. Results Arm lymphedema was associated with younger age at diagnosis (odds ratio, OR per year of age = 0.96; 95% confidence interval, CI = 0.93–0.99), positive history of hypertension (OR = 2.31; 95% CI = 1.38–3.88), obesity (OR for body mass index, BMI≥30 = 2.48; 95% CI = 1.05–5.84) and having had surgery where 10 or more lymph nodes were excised (OR = 2.16; 95% CI = 1.12–4.17). While Black women had higher prevalence of arm lymphedema than White women (28% vs. 21%), race was not associated with lymphedema risk in models adjusted for multiple factors (adjusted OR = 1.01; 95% CI = 0.63–1.63). Conclusion Risk of arm lymphedema did not differ significantly for Black and White women. Risk factors identified in this study offer opportunities for interventions (weight loss, control of blood pressure, use of sentinel node biopsy where possible) for reducing incidence of lymphedema or controlling the symptoms associated with this condition.     

Prognostic role of surgical margins in patients undergoing transoral robotic surgery after neo-adjuvant chemotherapy

PurposeTo define if positive and close surgical margins are associated to worse prognosis in patients who underwent transoral robotic surgery (TORS) after neoadjuvant chemotherapy (NCT).MethodsA retrospective cohort study was carried out at a tertiary referral center. The primary outcome was local-regional control (LRC), and the results were summarized with hazard ratios (HR) and 95% confidence intervals (CIs).ResultsA total of 308 patients (median age: 62.0, IQR: 55.0–68.2) were included. Univariable analysis showed a significant reduced LRC for patients with positive margins (HR = 1.82, 95% CI: 1.02–3.24). However, they were not associated with worse LRC after adjusting for adverse tumor variables (HR = 0.81, 95% CI: 0.40–1.65). ROC analysis was performed on 123 patients with negative margins (AUC: 0.54) measuring an optimal threshold of 1.25 mm (sensitivity = 60.0%; specificity = 50.5%). Univariable analysis showed non-significant differences between close and wide negative margins (HR = 1.44, 95% CI: 0.59–3.54).ConclusionsA positive surgical margin is not an independent predictor of tumor control and survival. A threshold of 1.25 mm was identified as the most appropriate to define close margins, but no difference was measured after distinguishing negative margins in close and wide margins.     

No significant association between the TP53 codon 72 polymorphism and breast cancer risk: a meta-analysis of 21 studies involving 24,063 subjects

Conflicting data have been published as to the possible association between polymorphism in codon 72 of the TP53 tumor suppressor gene and the risk of developing breast cancer. In order to address this question, we carried out a meta-analysis of 21 studies of and this polymorphism and breast cancer risk, which collectively included 12,601 cases and 11,462 controls. Studies were identified by searching the Medline, PubMed, Embase, and ISI Web of Knowledge databases. The strength of association between the TP53 codon 72 polymorphism and breast cancer risk was assessed by calculating crude OR values with 95% CIs, with pooled OR values calculated separately for three genetic inheritance models. We found no significant association between TP53 codon 72 polymorphism and breast cancer risk for either the codominant inheritance model (Pro/Arg vs. Pro/Pro: OR = 1.063, 95% CI = 0.967–1.169; Arg/Arg vs. Pro/Pro: OR = 1.245, 95% CI = 0.997–1.554), the dominant model (OR = 1.146, 95% CI = 0.979–1.340), or the recessive model (OR = 1.179, 95% CI = 1.020–1.362). Stratified analysis by ethnicity and source of controls similarly revealed no significant association for any of the genetic models. In summary, this meta-analysis provides strong evidence that the TP53 codon 72 polymorphism is not associated with the risk of developing breast cancer.     

TGFB1 L10P polymorphism is associated with breast cancer susceptibility: evidence from a meta-analysis involving 47,817 subjects

Published data on the association between TGFB1 L10P polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 30 studies including 20,401 cases and 27,416 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with TGFB1 10P allele when all studies were pooled into the meta-analysis (LP vs. LL: OR = 1.046, 95% CI = 1.003–1.090; dominant model: OR = 1.052, 95% CI = 1.012–1.095). In the subgroup analysis by ethnicity, statistically significantly elevated risk was found in Caucasians (dominant model: OR = 1.045, 95% CI = 1.001–1.091). When stratified by study design, statistically significantly elevated risk was found based on population-based studies (dominant model: OR = 1.076, 95% CI = 1.019–1.136). In conclusion, this meta-analysis suggests that the TGFB1 10P allele may be a low-penetrant risk factor for developing breast cancer. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.     

BRCA2 N372H polymorphism and breast cancer susceptibility: a meta-analysis involving 44,903 subjects

Published data on the association between BRCA2 N372H polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 22 studies including 22,515 cases and 22,388 controls were involved in this meta-analysis. Overall, no significant associations were found between BRCA2 N372H polymorphism and breast cancer risk when all studies pooled into the meta-analysis (NH versus NN: OR = 1.01, 95% CI = 0.97–1.05; HH versus NN: OR = 1.05, 95% CI = 0.97–1.13; dominant model: OR = 1.01, 95% CI = 0.98–1.05; and recessive model: OR = 1.05, 95% CI = 0.98–1.13). In the subgroup analysis by ethnicity, still no significant associations were found for Caucasians, Asians, or Africans. When stratified by study design, statistically significantly elevated risk was found for 372H allele based on population-based studies (HH versus NN: OR = 1.11, 95% CI = 1.01–1.21; dominant model: OR = 1.05, 95% CI = 1.00–1.10; recessive model: OR = 1.09, 95% CI = 1.00–1.18). In conclusion, this meta-analysis suggests that the BRCA2 372H allele may be a low-penetrant risk factor for developing breast cancer. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.     

Lack of association between HER2 codon 655 polymorphism and breast cancer susceptibility: meta-analysis of 22 studies involving 19,341 subjects

Epidemiological studies have investigated the association between HER2 codon 655 polymorphism and breast cancer susceptibility. However, the results are still inconclusive. To obtain a more precise estimation of the relationship, this meta-analysis was performed. A total of 22 studies including 9,209 cases and 10,132 controls were collected. The strength of association between HER2 codon 655 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 22 studies were pooled into the meta-analysis, there was no evidence for significant association between HER2 codon 655 polymorphism and breast cancer susceptibility (for Val/Ile vs. Ile/Ile: OR = 1.069, 95% CI = 0.976–1.172; for Val/Val vs. Ile/Ile: OR = 1.191, 95% CI = 0.922–1.538; for dominant model: OR = 1.093, 95% CI = 0.991–1.206; for recessive model: OR = 1.141, 95% CI = 0.902–1.444). In the subgroup analysis by the source of controls and ethnicity, no significant increased risk was found in all genetic models. However, the current results indicated the modest association between the HER2 Ile655Val polymorphism and Asian population (Val/Ile vs. Ile/Ile: OR = 1.207, CI = 1.006–1.450). In summary, the meta-analysis suggests that HER2 codon 655 polymorphism is not associated with the increased breast cancer risk.     

Absence of residual fluorescence in the surgical bed at near-infrared fluorescence imaging predicts negative margins at final pathology in patients treated with breast-conserving surgery for breast cancer

IntroductionPositive margins after breast-conserving surgery (BCS) for breast cancer (BC) remain a major concern. In this study we investigate the feasibility and accuracy of indocyanine green (ICG) fluorescence imaging (FI) for the in vivo assessment of surgical margins during BCS.Materials and methodsPatients with BC admitted for BCS from October 2015 to April 2016 were proposed to be included in the present study (NCT02027818). ICG (0.25 mg/kg) was intravenously injected at induction anesthesia and ICG-FI of the surgical beds was correlated with final pathology results.ResultsFifty patients consented to participate and thirty-five patients were retained for final analysis, 15 patients having been excluded for, respectively, incomplete video records data for signal to background ratio (SBR) calculation (11) and in situ tumors (4). The final pathological assessment of 35 breast specimens identified 5 (14.7%) positive margins. Intraoperative ICG-FI revealed hyperfluorescent signals in 15 (42.9%) patients and an absence of fluorescent signals in 20 (57.1%). Median SBR in patients with involved margins was 1.8 (SD 0.7) and was 1.25 (SD 0.6) in patients with clear margins (p = 0.05). The accuracy, specificity, positive and negative predictive value of ICG-FI for breast surgical margin assessment were 71%, 60%, 29% and 100%, respectively.ConclusionICG-FI of BC surgical beds has a high negative predictive value for surgical margin assessment during BCS. The absence of residual fluorescence in the surgical bed of patients with fluorescent tumors predicts negative margins at final pathology and allows the surgeon to avoid further intraoperative analysis.