Serum levels of HSP90 in the continuum of breast ductal and lobular lesions.

BACKGROUND: Heat-shock protein 90 (HSP90) is an abundant protein in mammalian cells. It interacts with a variety of proteins that play key roles in breast neoplasia. This is the first study to assess serum levels of HSP90 in atypical ductal hyperplasia (ADH), lobular neoplasia (LN), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and infiltrative lobular carcinoma (ILC). PATIENTS AND METHODS: Serum concentrations of HSP90 in women with benign (n=34), ADH (n=26), DCIS (n=30), IDC (n=29), LN (n=20) and ILC (n=9) lesions were determined with immunoenzymatic assays. For the evaluation of serum concentrations along the transition from benign through precursor and preinvasive to invasive lesion, the severity of diagnosis was treated as an ordinal variable. RESULTS: No significant association was demonstrated between serum HSP90 levels and the severity of the lesion in ductal and lobular series. The post hoc comparison between the lobular and ductal precursor lesions (i.e. ADH vs. LN) did not yield a statistically significant difference. Similarly, the post hoc comparison between the lobular and ductal invasive carcinomas (i.e. IDC vs. ILC) did not point to a statistically significant difference. CONCLUSION: This is the first study evaluating HSP90 serum levels in both lobular and ductal lesions of the breast. Contrary to published pathological findings according to which HSP90 exhibits significant variability along both series, such a finding was not replicated for the level of serum HSP90 concentrations.

Serum MMPs and TIMPs: may be predictors of breast carcinogenesis?

BACKGROUND: The involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in breast cancer has been documented on palpable lesions. This study aims to assess serum MMP1, MMP-2, TIMP-1, and TIMP-2 in atypical ductal hyperplasia (ADH), lobular neoplasia (LN), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) specifically in non-palpable mammographic breast lesions. METHODS: On women with benign (n=65), precursor [ADH (n=18) and LN (n=15)], preinvasive [DCIS (n=32)] and invasive [IDC (n=28)] lesions the serum concentrations of MMP-1, MMP-2, TIMP-1, TIMP-2, TPS, and TPA were determined with immunoenzymatic assays. All women had non-palpable mammographic breast lesions of less than 10mm in diameter, as estimated on the mammographic views. Statistical analysis followed. RESULTS: TIMP-2 serum concentrations were positively associated with the severity of the lesion. On the contrary, MMP-2 levels were marginally negatively associated with severity; as evident, the MMP-2/TIMP-2 ratio significantly decreased along with severity. Regarding TIMP-1, TPS, TPA, and TIMP-1/TIMP-2, no significant associations were demonstrated. MMP-2 and the MMP-2/TIMP-2 ratio were significantly higher in the LN subgroup versus the ADH subgroup. CONCLUSION: TIMP-2 and MMP-2/TIMP-2 ratio may exhibit meaningful changes along with progression of lesions. Extracellular cell matrix remodeling in ductal and lobular lesions may follow distinct patterns.

Volume of blood suctioned during vacuum-assisted breast biopsy predicts later hematoma formation.

BACKGROUND: To evaluate whether the volume of blood suctioned during vacuum-assisted breast biopsy (VABB) is associated with hematoma formation and progression, patient's age and histology of the lesion. FINDINGS: 177 women underwent VABB according to standardized protocol. The volume of blood suctioned and hematoma formation were noted at the end of the procedure, as did the subsequent development and progression of hematoma. First- and second-order logistic regression was performed, where appropriate. Cases with hematoma presented with greater volume of blood suctioned (63.8 +/- 44.7 cc vs. 17.2 +/- 32.9 cc; p < 0.001, Mann-Whitney-Wilcoxon test for independent samples, MWW); the likelihood of hematoma formation was increasing till a volume equal to 82.6 cc, at which the second-order approach predicts a maximum. The volume of blood suctioned was positively associated with the duration of the procedure (Spearman's rho = 0.417, p < 0.001); accordingly, hematoma formation was also positively associated with the latter (p = 0.004, MWW). The volume of blood suctioned was not associated with patients' age, menopausal status and histopathological diagnosis. CONCLUSION: The likelihood of hematoma is increasing along with increasing amount of blood suctioned, reaching a plateau approximately at 80 cc of blood lost.

Breast ductal endoscopy: how many procedures qualify?

BACKGROUND: Breast ductal endoscopy is a relatively new diagnostic method with ever growing importance in the work-up of patients with bloody nipple discharge. The ability to perform ductal endoscopy is very important and useful for breast fellows. Learning curve in breast ductal endoscopy remains a terra incognita, since no systematic studies have addressed this topic. The purpose of this study is to determine the point (number of procedures during training) beyond which ductal endoscopy is successfully performed. FINDINGS: Ten breast fellows received training in our Breast Unit. For the training process, an ex vivo model was adopted. Fellows were trained on 20 surgical specimens derived from modified radical mastectomy for breast cancer. The target of the education program was to acquire proficiency in performing ductoscopy. The achievement of four consecutively successful ductal endoscopies was determined as the point beyond which proficiency had been achieved. The number of procedures needed for the achievement of proficiency as defined above ranged between 9 and 17 procedures. The median value was 13 procedures; i.e. 50% of trainees had achieved proficiency at the 13th procedure or earlier. CONCLUSION: These pilot findings point to approximately 13 procedures as a point beyond which ductal endoscopy is successfully performed; studies on a larger number of fellows are nevertheless needed. Further research, focusing on the learning curves of different training models of ductal endoscopy, seems desirable.