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Introduction: Fibroepithelial breast lesions are biphasic neoplasms characterized by proliferation of both stromal and epithelial cells. They encompass a spectrum of tumors ranging from benign fibroadenoma to potentially fatal malignant phyllodes tumor, with tumors of borderline clinical significance in-between. It is important to correctly characterize each lesion, as this defines management and thus risk of local recurrence and potential distant metastasis in case of malignancy. Case Report: A 48-year-old woman presented with a palpable retro-areolar lump in the left breast. After core biopsy, the initial pathology report initiated tumorectomy. When the final report stated a borderline phyllodes tumor with incomplete resection, reintervention was needed with wide surgical margins to avoid local recurrence. The local re-excision showed scarring and steatonecrosis as a result of the previous procedure, but no residual lesion. Consequently, there was no need for further surgical intervention. Conclusion: Fibroepithelial lesions (FEL) of the breast are a wide variety of lesions with distinct management based on the exact pathologic character. Core needle biopsy poses a risk of sampling error due to intratumoral heterogeneity that sometimes may be found in cellular FEL. As a consequence, upgrading at the time of the excision specimen can frequently occur with need of reintervention.

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.

Introduction: The objective of the sentinel lymph node (SLN) procedure in breast cancer is to perform an accurate axillary staging and provide good local control, while sparing the patients the morbidity of an axillary lymph node dissection (ALND). Since its routine clinical use, questions have been raised concerning the upstaging of a subgroup of node-negative patients and an increase in the overall percentage of node-positive patients. The goal of our study was to investigate the impact of the SLN procedure on the detection of positive lymph nodes. Patients and methods: We included 1119 consecutive breast cancer patients from one center (2007-2009) who underwent primary surgery for a breast cancer smaller than 5 cm diameter without clinical involvement of axillary lymph nodes. 31 patients had a bilateral breast cancer. Logistic regression models were used to analyze the effect of various predictors on the presence of positive lymph nodes. First, we fitted univariable models for a number of predictors of which the relationship with lymph node involvement was to be expected. (multifocality, tumor location in the breast, tumor size, LVI, ER, PR, Her-2, tumor grade, age and histologic subtype). In a second stage, we fitted a multivariable model including the procedure (SLN biopsy or ALND) and the predictors that have been shown to be related to lymph node involvement in univariable analysis or for which this relationship has been suggested in the literature. The probability of finding positive lymph nodes was thus calculated in both groups correcting for relevant predictors of lymph node involvement. Results: The SLN biopsy group includes 830 patients, the ALND group 320. Tumors in the ALND group are larger (mean 26.65 mm versus 18.43mm) and more frequently multifocal (24.44% versus 8.19%). 33% of patients in the ALND group were lymph node positive, 28% in the SLN procedure group. Univariable and multivariable analyses revealed that LVI, tumor size and multifocality are the most significant predictors of lymph node involvement (table 1). The AUC for the multivariate model is 0.754. By comparing ALND en SLN biopsy an odds ratio (OR) of 0.7635 (95% confidence interval: 0.5334−1.0930) is observed, suggesting a higher probability of finding positive lymph nodes with SLN procedure. However, the difference between the procedures is not significant (p= 0.1404). Conclusion: For comparable tumors, the chance of detecting positive lymph nodes is not lower when applying SLN procedure compared to ALND. The results even point in the direction of a higher detection rate with SLN. However, care should be taken in making this conclusion given a non-significant result. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-40.

Purpose. Lymph node involvement is the most important prognostic factor in breast cancer. It is a multifactorial event determined by tumour and patient characteristics. Several predictors of axillary lymph node metastasis (ALNM) in breast cancer have been described. The purpose of this study was to determine clinical and pathological factors predictive for ALNM in patients with early breast cancer and to build a model to portend lymph node involvement. Methods. We evaluated 1300 consecutive patients surgically treated in our institution (2007-2009) for cT1-T2 invasive breast cancer. The patient and tumour characteristics evaluated included: age at diagnosis, number of foci, histologic grade, location, tumour size, histologic subtype, lymphovascular invasion (LVI), estrogen-receptor (ER), progesterone-receptor (PR) and Her2 status. Univariate and multivariate analyses were performed. Factors significantly associated with lymph node metastasis by univariate analysis and histologic subtype were included in the multivariate model. We validated our model with the same 1300 patients on the basis of a multivariable logistic regression model containing the variables, using a correction factor. Results. By univariate analysis, the incidence of ALNM was significantly higher in patients with a tumour with LVI (P < 0.0001), larger tumours (P < 0.0001), tumours with a higher histologic grade (P < 0.0001), tumours located retroareolar or lateral in the breast (P < 0.0001), tumours with multiple foci (P = 0.0002) and in patients who underwent an axillary lymph node dissection. We found no effect of ER/PR nor HER-2 status. By multivariate analysis, lymph node involvement was significantly associated with the presence of lymphovascular invasion (P < 0.0001), larger tumour size (P < 0.0001), axillary lymph node dissection (P = 0.0003), retroareolar and lateral tumour location in the breast (P = 0.0019) and the presence of multiple foci (P = 0.0155). The discrimination of the model, calculated by the area under the curve (AUC), was 0.778. Conclusions. LVI and tumour size emerged as most powerful independent predictors of ALNM. A model with an AUC of 0.50 is equivalent to the toss of a coin, a model with an AUC > 0.70 is considered as good. In conclusion, our result is not perfect in discrimination which raises further questions. It is clear that underlying mechanisms of ALNM remain to be elucidated. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-21.

Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1 of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report. © 2015 © The Author 2015. Published by Oxford University Press.